DEPARTMENT OF HEALTH AND HUMAN … Workforce ... Centers for Disease Control and Prevention, National Institute for Occupational Safety and Health, DHHS (NIOSH) Publication 2014–106

Protecting the

Nanotechnology Workforce

NIOSH Nanotechnology Research and Guidance

Strategic Plan, 2013–2016

DEPARTMENT OF HEALTH AND HUMAN SERVICESCenters for Disease Control and PreventionNational Institute for Occupational Safety and Health

Protecting the Nanotechnology WorkforceNIOSH Nanotechnology Research and GuidanceStrategic Plan, 2013–2016

DEPARTMENT OF HEALTH AND HUMAN SERVICES Centers for Disease Control and Prevention National Institute for Occupational Safety and Health

ii | Protecting the Nanotechnology Workforce

This document is in the public domain and may be freely copied or reprinted.

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Suggested CitationNIOSH [2013]. Protecting the nanotechnology workforce: NIOSH nanotechnology research and guidance strategic plan, 2013–2016. Cincinnati, OH: U.S. Department of Health and Human Ser-vices, Centers for Disease Control and Prevention, National Institute for Occupational Safety and Health, DHHS (NIOSH) Publication 2014–106.

DHHS (NIOSH) Publication No. 2014–106

December 2013

Safer • Healthier • PeopleTM

Protecting the Nanotechnology Workforce | iii

ForewordThe National Institute for Occupational Safety and Health (NIOSH) is pleased to present Pro-tecting the Nanotechnology Workforce: NIOSH Nanotechnology Research and Guidance Strategic Plan, 2013–2016. This plan updates the November 2009 strategic plan with knowledge gained from results of ongoing research, as described in the 2012 report Filling the Knowledge Gaps for Safe Nanotechnology in the Workplace: A Progress Report from the NIOSH Nanotechnology Research Center, 2004–2011. The NIOSH Nanotechnology Research Program follows a comprehensive plan that is managed as a matrix structure across NIOSH and supports multiple sectors in the National Occu-pational Research Agenda (NORA).

Nanotechnology provides many opportunities for advancing the economic value and impact of new U.S. technologies and products as it expands into every industrial sector. Today, nanomaterials are found in hundreds of products, ranging from cosmetics, to clothing, to industrial and biomedical applications. The potential benefits of nanotechnology are huge, and these benefits should be re-alized by society. However, there is ongoing concern that the full potential of the societal benefits may not be realized if research efforts are not undertaken to determine how to best manage and control the potential occupational safety and health hazards associated with the handling of these nanomaterials.

The research conducted over the past 8 years has proven that NIOSH is a global leader in promot-ing the responsible development of nanotechnology. NIOSH has built business partnerships, estab-lished itself as a key player in nanotoxicology, published precautionary guidance (Approaches to Safe Nanotechnology: Managing the Safety and Health Concerns Associated with Engineered Nanomaterials), and issued recommended exposure limits for nanoscale titanium dioxide and for carbon nanotubes and nanofibers.

This NIOSH Nanotechnology Research and Guidance Strategic Plan is the roadmap being used to ad-vance basic understanding of the toxicology and workplace exposures involved so that appropriate risk management practices can be implemented during discovery, development, and commercializa-tion of engineered nanomaterials. NIOSH will strive to remain at the forefront of developing guid-ance that supports and promotes the safe and responsible development of such a promising tech-nology.

John Howard, M.D.Director, National Institute for Occupational

Safety and HealthCenters for Disease Control and Prevention

iv | Protecting the Nanotechnology Workforce

Executive SummaryNanotechnology—the manipulation of matter on a near-atomic scale to produce new materials and devices—has the ability to transform many industries, from medicine to manufacturing, and the products they produce. By 2020, the National Science Foundation estimates, nanotechnology will have a $3 trillion impact on the global economy and employ 6 million workers in the manufac-ture of nanomaterial-based products, of which 2 million may be manufactured in the United States [NSF 2011]. Nanomaterials may present new challenges to understanding, predicting, and manag-ing potential health risks to workers.

Many knowledge gaps still remain on how to work safely with all of these materials. Through stra-tegic planning, research, partnering with stakeholders, and making information widely available, the National Institute for Occupational Safety and Health (NIOSH) is working to continue to provide national and world leadership in providing solutions that will prevent work-related illness and injury.

Nanotechnology and NIOSH ResearchNanotechnology and the commercialization of products and devices containing engineered nano-materials could help address critical global problems concerning energy, transportation, pollution, health, and food. The potential benefits of nanotechnology are huge, and these benefits should be realized. Nonetheless, there is concern that the full potential of the societal benefits may not be re-alized if cautions about the adverse human health effects are not heeded and concerns are not hon-ored. Timely, targeted research is needed to define hazards, exposures, and risks and to provide guidance for safe handling of nanomaterials. A concerted effort by industry, academia, labor, the professions, and government is needed to identify and address the knowledge gaps in a transpar-ent and credible process that coincides with development of this new technology. NIOSH is play-ing an active part in this process by supporting the development of a broad spectrum of research and prevention strategies for health and safety hazards related to nanotechnology. In a series of re-ports [NIOSH 2007, 2009a, 2012a], NIOSH has summarized its progress in conducting nano-technology research and recommending risk management strategies (see http://www.cdc.gov/niosh/topics/nanotech/). NIOSH investigators have identified adverse health effects in animals exposed to various engineered nanomaterials; assessed exposure of workers; initiated epidemiologic research; and provided guidance on control technologies and medical surveillance. There are many questions still to be answered. A vast number of potential new nanomaterials are possible and could result in a seemingly limitless combination of physicochemical factors. There is need for an expeditious ap-proach to controlling exposure to the large number of nanomaterials in science and commerce now and in the future. Moreover, the advanced nanomaterials under development are likely to have ad-ditional potentially hazardous characteristics that will need to be addressed [Murashov et al. 2012].

NIOSH Nanotechnology Research Center (NTRC)The NIOSH Nanotechnology Research Center (NTRC) was established in 2004 to coordinate nanotechnology research across the institute. Ten critical areas of research were identified, each hav-ing at least one key scientist serving as a coordinator. The NTRC and its steering committee of crit-ical area coordinators are responsible for developing and guiding NIOSH scientific and organiza-tional plans in nanotechnology health and safety research.

http://www.cdc.gov/niosh/topics/nanotech/

http://www.cdc.gov/niosh/topics/nanotech/

Protecting the Nanotechnology Workforce | v

Strategic PlanThe development of nanotechnology has reached a point where it is being widely applied, and nu-merous nanomaterials and nano-enabled products are in commerce. Nanotechnology has the po-tential to provide great benefit to society, but it must be developed responsibly. This responsibili-ty involves addressing any adverse human and environmental impacts of the technology associated with engineered nanomaterials (ENMs). Workers are among the first people in any society to be exposed to the potential health hazards caused by the products of new technology, and their expo-sure to any new material is often greater than for the general population. Therefore, worker safety and health can be seen as the core of responsible development (Figure 1).

Through its strategic plan for fiscal years (FY) 2013–2016, NIOSH will marshal its resources and partner with others efficiently and effectively to advance efforts to protect the nanotechnology workforce. With the input of a broad range of stakeholders in government, academia, and the pri-vate sector, NIOSH will continue to operate under a strategic plan for nanotechnology research and guidance. The most recent previous version was published in November 2009 and included research plans through FY 2012 (see http://www.cdc.gov/niosh/docs/2010-105/).

Figure 1. The core of responsible development of nanotechnology.

Significantbenefits to

society

Responsible development ofthe technology

Nanomaterial worker safety

and health

http://www.cdc.gov/niosh/docs/2010-105/

vi | Protecting the Nanotechnology Workforce

This document presents the NTRC Strategic Plan for FY2013–FY2016. The strategic plan also highlights how the critical research and guidance efforts of NIOSH align with and support the comprehensive Environmental, Health, and Safety Research Strategy needs of the National Nan-otechnology Initiative. For the period FY2013–FY2016, NIOSH will continue to fill information and knowledge gaps that address the five NIOSH NTRC strategic goals:

1. Increase understanding of new hazards and related health risks to nanomaterial workers.2. Expand understanding of the initial hazard findings of engineered nanomaterials.3. Support the creation of guidance materials to inform nanomaterial workers, employers,

health professionals, regulatory agencies, and decision-makers about hazards, risks, and risk management approaches.

4. Support epidemiologic studies for nanomaterial workers, including medical, cross-sectional, prospective cohort, and exposure studies.

5. Assess and promote national and international adherence with risk management guidance.

To address these strategic goals and promote the responsible development of engineered nanoma-terials, the strategic plan will expand research activities in 10 NTRC critical areas: toxicity and in-ternal dose; measurement methods; exposure assessment; epidemiology and surveillance; risk as-sessment; engineering controls and personal protective equipment (PPE); fire and explosion safety; recommendations and guidance; global collaborations; and applications.

Protecting the Nanotechnology Workforce | vii

ContentsForeword . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . iiiExecutive Summary . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . ivAcknowledgments . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . ixAbbreviations . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . x

1 INTRODUCTION 1

1.1 Background . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 11.2 Mission of NIOSH . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 11.3 NIOSH Logic Model . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 3

2 INPUTS 7

2.1 Nature of Nanomaterials . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 72.2 Nature of the Nanomaterial Workplace . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 7 2.3 Customer and Stakeholder Input. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 7 2.4 NIOSH Research Capabilities . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 92.5 NIOSH Partnerships . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 9

3 ACTIVITIES 11

3.1 NIOSH Nanotechnology Research Center (NTRC) . . . . . . . . . . . . . . . . . . . . . . . . 113.2 NTRC Steering Committee . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 113.3 Current NIOSH NTRC Intramural Nanotechnology Research Activities. . . . . . . . 11

3.3.1 Evaluation of the nanotechnology research program . . . . . . . . . . . . . . . . . . . . 11

3.4 Current NIOSH Extramural Nanotechnology Research Activities. . . . . . . . . . . . . . 12

4 GOALS 13

4.1 Address Each Element in the Risk Management Continuum . . . . . . . . . . . . . . . . . 134.2 Identification of NTRC Data Needs for Knowledge Gaps . . . . . . . . . . . . . . . . . . . . 134.3 Coalescing Priorities for NIOSH NTRC Research and Guidance for FY2013–FY2016 . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 164.4 Coordination with the National Nanotechnology Initiative . . . . . . . . . . . . . . . . . . . 184.5 Proposed NIOSH NTRC Research . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 18

5 OUTPUTS 29

5.1 NIOSH Publications on Nanotechnology Since 2009 . . . . . . . . . . . . . . . . . . . . . . . 295.2 NIOSH Peer-Reviewed Publications . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 305.3 Sponsored Conferences . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 305.4 Presentations . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 30

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6 RESEARCH TO PRACTICE (r2p) 31

6.1 Capacity Building through Technical Assistance. . . . . . . . . . . . . . . . . . . . . . . . . . . . 31

7 Intermediate Customers and Intermediate Outcomes 33

7.1 Federal Government Agencies. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 337.2 Standards Development Organizations . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 337.3 Industry, Labor, and Academia . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 337.4 Professional Organizations . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 337.5 Research Collaborations . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 347.6 International Activities . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 34

8 OUTCOMES 35

References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 37Appendix A: Comprehensive Chart of the NNI 2011 EHS Research Needs . . . . . . . . . . . . . 39Appendix B: Timeline for NIOSH Nanotechnology Research . . . . . . . . . . . . . . . . . . . . . . . . 49

Protecting the Nanotechnology Workforce | ix

AcknowledgmentsThis report was developed by the scientists and staff of the National Institute for Occupation-al Safety and Health (NIOSH) who participate in the NIOSH Nanotechnology Research Cen-ter (NTRC). Paul Schulte is the manager and Charles Geraci is the coordinator of the NIOSH cross-sector program. Special thanks go to Laura Hodson for writing and organizing the report. Others who contributed substantially to the report include Vincent Castranova, Teh-hsun (Bean) Chen, Matthew Dahm, Kevin Dunn, Douglas Evans, Pengfei Gao, Mark Hoover, Eileen Kuempel, Kenneth Martinez, Vladimir Murashov, Mary Schubauer-Berigan, Aleksandr Stefaniak, Douglas Trout, and Leonid Turkevich.

The NIOSH NTRC acknowledges the contributions of Sarah Earl, Gino Fazio, Rachel Thieman, and Vanessa Williams for their graphic design and production services, and Seleen Collins for ed-iting the report. In addition, it expresses special appreciation to these individuals and organizations for their reviews and comments:

Carol Rice, Ph.D., CIH University of Cincinnati Cincinnati, OH

Michael Kosnett, M.D. University of Colorado Denver, CO

James Bonner, Ph.D. North Carolina State University Raleigh, NC

Lindsey Darrow, Ph.D. Rollins School of Public Health Atlanta, GA

Ellen Eisen, Ph.D. University of California, Berkeley Berkeley, CA

Michael Ellenbecker, Ph.D. University of Massachusetts, Lowell Lowell, MA

Lawrence Gibbs, M.Ed., M.P.H., CIH Stanford University Stanford, CA

Steven Gordon, Ph.D. 3M St. Paul, MN

Bruce Lippy, Ph.D., CIH, CSP CPWR, The Center for Construction Research and Training Baltimore, MD

Günter Oberdörster, D.V.M., Ph.D. University of Rochester Medical Center Rochester, NY

Michele Ostraat, Ph.D. RTI International Research Triangle Park, NC

Gurumurthy Ramachandran, Ph.D. University of Minnesota Minneapolis, MN

Darius Sivin, Ph.D. United Auto Workers Washington, D.C.

Keith A. Swain, B.S. Dupont Wilmington, DE

David Warheit, Ph.D. Dupont Newark, DE

John Weaver, B.S. Purdue University West Lafayette, IN

x | Protecting the Nanotechnology Workforce

AbbreviationsAFL-CIO American Federation of Labor and Congress of Industrial OrganizationsAIHA American Industrial Hygiene AssociationANSES The French Agency for Food, Environmental and Occupational Health and SafetyANSI American National Standards InstituteASSE American Society of Safety EngineersASTM American Society for Testing and Materials (currently ASTM International)CNT carbon nanotubeCPSC Consumer Product Safety CommissionDHHS Department of Health and Human ServicesDOT Department of TransportationEHS environment, health and safetyENM engineered nanomaterialEPA U.S. Environmental Protection AgencyEU European UnionFMSH Federal Mine Safety and HealthFY fiscal yearICOH International Commission on Occupational HealthICON International Council on NanotechnologyIEC International Electrotechnical CommissionILO International Labour OrganizationISEA International Safety Equipment AssociationISO International Organization for StandardizationMSHA Mine Safety and Health AdministrationNanoBCA Nanobusiness Commercialization AssociationNCER National Center for Environmental ResearchNEHI Nanotechnology Environmental and Health ImplicationsNFPA National Fire Protection AssociationNIEHS National Institute of Environmental Health SciencesNIH National Institutes of HealthNIOSH National Institute for Occupational Safety and Health NIST National Institute of Standards and TechnologyNNI National Nanotechnology InitiativeNORA National Occupational Research Agenda

Protecting the Nanotechnology Workforce | xi

NSC National Safety CouncilNSF National Science FoundationNTRC Nanotechnology Research CenterOECD Organization for Economic Cooperation and DevelopmentOEP Office of Extramural ProgramsOSH occupational safety and healthOSHA Occupational Safety and Health AdministrationPPE personal protective equipmentPtD Prevention through Designr2p Research to PracticeTNO The Netherlands Organization for Applied Scientific ResearchUN United NationsWHO World Health Organization

Protecting the Nanotechnology Workforce | 1

1 INTRODUCTION

1.1 BackgroundNanotechnology is a system of innovative meth-ods to control and manipulate matter at near-atomic scale to produce new materials, structures, and devices. Nano-objects are nanomaterials that have at least one dimension less than 100 nano-meters [ISO 2008]. Nanoparticles are a specific class or subset of these nano-objects, having three dimensions that are less than 100 nanometers. Nanoparticles exhibit unique properties because of their nanoscale dimensions. Nanotechnolo-gy offers the potential for tremendous improve-ment and advances in the development of com-mercial products that may benefit society, such as integrated sensors, semiconductors, medical imaging, drug delivery systems, structural mate-rials, sunscreens, cosmetics, and coatings. Nano-technology is one of the most enabling technolo-gies across the world. By 2020, the global market for nanotechnology-related products is predicted to reach $3 trillion and employ 2 million work-ers in the United States alone [NSF 2011]. A review of the 2013 version of the Nanowerk nanomaterials database (http://www.nanowerk.com/phpscripts/n_dbsearch.php) revealed more than 3,000 commercially available nanomaterials.

However, the properties of engineered nanopar-ticles (e.g., size, surface area, reactivity) that yield many improvements in commercial products may also pose health risks. Increasing numbers of workers are potentially exposed to nanoma-terials in research laboratories, start-up compa-nies, production facilities, and operations where nanomaterials are processed, used, disposed, or recycled. The challenge is to determine wheth-er the nature of intentionally produced (engi-neered) nanostructured materials and devic-es presents new occupational safety and health risks. At the same time, there is a need to ad-dress how the benefits of nanotechnology can

be realized while the risks are proactively min-imized.

Efforts across multiple federal agencies and the private and academic sectors are fostering the development and use of nanotechnology. In 2001, the President’s Council of Advisors on Science and Technology collaborated with the interagency National Science and Technology Council to create the National Nanotechnol-ogy Initiative (NNI) [NNI 2001]. This initia-tive supports basic and applied research in nan-otechnology to create new nanomaterials and to disseminate new technical capabilities to indus-try. The purpose of the NNI is to facilitate sci-entific breakthroughs and maintain U.S. com-petitiveness in nanoscience. A stated goal of this interagency program is to ensure that nanotech-nology research leads to the responsible devel-opment of beneficial applications by giving high priority to research on human health, environ-mental issues, and societal implications related to nanotechnology.

1.2 Mission of NIOSHIn the Occupational Safety and Health Act of 1970 (OSH Act, Public Law 91-596) and the Federal Mine Safety and Health Act of 1977 (FMSH Act, Public Law 95-164), Congress de-clared that the intent of these acts was to ensure, insofar as possible, safe and healthful working conditions for every working man and woman, to preserve our human resources. In these acts, NIOSH is given the responsibility for recom-mending occupational safety and health stan-dards and defining exposure levels that are safe for various periods of employment. These in-clude (but are not limited to) the exposures at which no worker will suffer diminished health, functional capacity, or life expectancy as a result

http://www.nanowerk.com/phpscripts/n_dbsearch.php

http://www.nanowerk.com/phpscripts/n_dbsearch.php

2 | Protecting the Nanotechnology Workforce

of his or her work experience. By means of crite-ria documents and other publications, NIOSH communicates these recommended standards to the Occupational Safety and Health Admin-istration (OSHA), the Mine Safety and Health Administration (MSHA), and others in the oc-cupational safety and health community.

Under the OSH Act, NIOSH is charged with conducting “research, experiments, and dem-onstrations relating to occupational safety and health” and with developing “innovative meth-ods, techniques, and approaches for dealing with [those] problems.” The act specifies target areas of research that include identifying crite-ria for setting worker exposure standards and exploring problems created by new technology in the workplace. In an amendment to the act, NIOSH was given responsibility for conduct-ing training and education “to provide an ade-quate supply of qualified personnel to carry out the purposes of the Act” and for assisting em-ployers and workers with applying methods to prevent occupational injuries and illness (Sec-tion 21 of the OSH Act).

NIOSH has over 40 years of experience in con-ducting research and formulating recommen-dations for occupational safety and health. During this period, NIOSH has developed considerable expertise in measuring, character-izing, and evaluating new processes and new materials by conducting quantitative expo-sure assessments and evaluating health effects. NIOSH also has expertise in developing expo-sure control systems and prevention strategies as well as experience in conducting risk assess-ments and recommending effective risk man-agement practices.

In 2003, NIOSH became a member of the Na-noscale Science, Engineering, and Technology (NSET) Subcommittee of the National Sci-ence and Technology Council. As a member, NIOSH participates in (1) identifying critical issues related to possible hazards of nanoma-terials, (2) protecting worker safety and health in this emerging technology, and (3) developing a strategic plan to address such issues and

recommend prevention strategies for the safe handling and use of nanomaterials.

In 2004, NIOSH created the Nanotechnology Research Center (NTRC) to identify critical issues, create a strategic plan for investigating these issues, coordinate the NIOSH research effort, develop research partnerships, and dis-seminate information gained. The NTRC com-prises nanotechnology-related activities and projects supported by approximately 50 sci-entists in various NIOSH divisions and lab-oratories. Through the NTRC, NIOSH has identified 10 critical research areas for nano-technology research and communication. These 10 critical research areas, updated for FY2013–FY2016, are toxicity and internal dose; mea-surement methods; exposure assessment; ep-idemiology and surveillance; risk assessment; engineering controls and personal protec-tive equipment (PPE); fire and explosion safe-ty; recommendations and guidance; global col-laborations; and applications. By conducting a complete plan of research in these critical areas in a coordinated, concurrent manner, NIOSH is comprehensively addressing the information and knowledge gaps necessary to protect work-ers and responsibly move nanotechnology for-ward so that its far-reaching benefits may be re-alized.

The NIOSH NTRC is working strategical-ly to fill nanomaterial occupational safety and health knowledge gaps through active intra-mural and extramural research programs and collaborations. Extramural research is carried out through the NIOSH Office of Extramu-ral Programs (OEP), in which nanotechnolo-gy research (through R01, K01, R03, R21, and R43/44 grant mechanisms) is funded to in-crease the knowledge of nanotechnology and engineered nanomaterials (ENMs) as they re-late to occupational safety and health. Research areas supported by the NIOSH OEP include emission and exposure assessment methods for nanoparticles in the workplace, toxicology of ENMs, and use of nanotechnology for the development of sensors. NIOSH is committed


to conducting and supporting studies that will improve scientists’ abilities to identify potential occupational health effects of nanomaterials. NIOSH will facilitate the translation of those findings into effective workplace practices.

NIOSH reported on the progress of the NTRC in Filling the Knowledge Gaps for Safe Nano-technology in the Workplace (Figure 2). This re-port presents the program accomplishments of the NTRC from its inception in 2004 through 2011.

The NIOSH NTRC continues to be part of the U.S. leadership on the International Organiza-tion for Standardization (ISO) TC 229 Nano-technology Working Group on Health, Safe-ty, and the Environment and continues to work with the World Health Organization (WHO) collaborating centers on global projects of in-formation dissemination and communication. Through these collaborations, the NIOSH NTRC assists in developing risk communica-tions on the safe handling of nanomaterials.

1.3 NIOSH Logic ModelNIOSH receives input on identifying and ad-dressing occupational safety and health prob-lems through a logic model (i.e., a process) in which the seriousness of the problem or haz-ard is evaluated, the type and level of research needed are determined, and a plan and process for communicating the research outcomes are formulated. The overall NIOSH logic model (Figure 3) has a conventional horseshoe shape, with the operational upper branch proceeding from inputs to mission relevant outcomes and the strategic lower branch supporting those op-erations through a process of measurable goals and management objectives. The two branches are correlated and are subject to external factors.

The NIOSH operational model (Figure 4) for conducting research adheres to the logic mod-el in the acquisition and analysis of inputs from customers/stakeholders (production inputs) and internal/external research capabilities (planning inputs) to determine and prioritize research.

Figure 2. The cover of DHHS (NIOSH) Publication No. 2013–101, the progress report of the NTRC.


Intramural and extramural researchers present their project proposals, which receive appropri-ate internal and external review and are funded on the basis of merit. The conduct of research (activities) produces “outputs” such as guid-ance documents and reports that address ef-fective risk management practices, worker and employer education, and new technologies for assessing and controlling workplace hazards. NIOSH outputs are transferred directly to the final customers and stakeholders (who imple-ment improvements in workplace safety and health) or to intermediate customers (who uti-lize NIOSH outputs to produce intermediate outcomes). These intermediate outcomes, such

Figure 3. Schematic of the overall NIOSH logic model.

as training programs, regulations, and occupa-tional standards, are used to advance workplace safety and health. Since NIOSH is not a regu-latory agency, it relies heavily on efforts by in-termediate and final customers to achieve ulti-mate outcomes in the form of workplace safety and health improvements. The effectiveness in achieving these outcomes is influenced at all stages of the program operation by both exter-nal factors (such as economic and social con-ditions) and the regulatory environment. Re-sults of NIOSH-funded research and customer feedback (intermediate and final outcomes) con-tribute to the subsequent rounds of program planning.

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2 INPUTS

2.1 Nature of NanomaterialsThe universe of nanomaterials is potentially large because of the array of possible combina-tions of physicochemical parameters, impurities, and manufacturing and production conditions (Figure 5). NIOSH recognizes the extensive di-versity and number of nanomaterials and the even larger number of applications for those materials. Consequently, it continues to use ap-proaches that allow for a holistic view of nano-materials and development of priorities that will be beneficial to many workers.

2.2 Nature of the Nanomaterial Workplace

Worker exposure to nanomaterials may occur along the life cycle of the nanomaterial, from re-search through scale-up, manufacturing, prod-uct development, use, and end of life (Figure 6).

Each of the functional areas represents work-places with different potential exposure scenar-ios and risks. NIOSH continues to focus on the wide array of workplaces where exposure to nanomaterials may occur.

2.3 Customer and Stakeholder Input

To direct its research and fulfill its responsi-bilities under the OSH Act and the FMSH Act, NIOSH has relied on input from OSHA and MSHA, workers, employers, trade associ-ations, unions, occupational safety and health practitioners and researchers, and the general public. NIOSH also seeks input through for-mal committees, such as the NIOSH Board of Scientific Counselors, the National Advi-sory Committee on Occupational Safety and Health, and the Mine Safety and Health Re-search Advisory Committee. It also receives

Figure 5. The wide variety of physicochemical parameters of engineered nanomaterials [Schulte et al. 2009].


Figure 6. The life cycle of nanomaterials [Schulte et al. 2008a].

Research Laboratories

Start-Up/Scale-Up Operations

Manufacturing/Production

Incorporation in Products

Recycling

Warehousing/MaintenanceWaste Handling

TransportWarehousing/Maintenace

Warehousing/MaintenanceTransportWaste handling

Maintenance of ProductsManipulation of ProductsApplication of Products-Medical Delivery

Disposal/End of Life


input through ad hoc mechanisms such as the NIOSH Web site (www.cdc.gov/niosh), a toll-free telephone line (1-800-CDC-INFO), per-sonal contacts with occupational safety and health professionals, and participation in pro-fessional conferences and interagency commit-tees. In addition, NIOSH provides stewardship of the National Occupational Research Agenda (NORA) (http://www.cdc.gov/niosh/nora), which is a framework to guide occupational safety and health research into the new millennium—not only for NIOSH but for the entire occupation-al safety and health community.

NIOSH continues to be a participating and partnering agency in the National Nanotech-nology Initiative (NNI) and provides occu-pational health and safety expertise in sup-port of the U.S. Government’s Strategic Plan for Nanotechnology Environmental, Health, and Safety Research [NNI 2011]. NIOSH is co-leader of the NNI Nanotechnology En-vironmental and Health Implications Work-ing Group (NEHI) and contributed to the de-velopment of the 2011 NEHI Environmental, Health, and Safety (EHS) Research Strategy. The 2011 NEHI EHS research strategy iden-tified five core nanotechnology EHS research categories: (1) nanomaterial measurement in-frastructure, (2) human exposure assessment, (3) human health, (4) environment, and (5) risk as-sessment and management methods (Appendix A) [NNI 2011]. NIOSH provided significant input for the strategy and was the lead agen-cy for developing recommendations on human exposure assessment. The NNI EHS research strategy focuses on the use of science-based risk analysis and risk management to protect public health and the environment while fostering the technological advancements that benefit soci-ety. NIOSH has strived to keep the overarching research activities of the NTRC nanotechnol-ogy strategic plan (Section 4.3) consistent with the NNI EHS research strategy.

The NIOSH NTRC also fosters stakeholder in-put with trade associations, professional associ-ations, labor, nongovernmental organizations,

and a number of private nanomaterial compa-nies. These collaborations have provided exper-tise and resources critical for reviewing research activities and for developing and disseminating health and safety information on engineered nanoparticles. Some of the ongoing NTRC stakeholders are the American Industrial Hy-giene Association (AIHA), American Soci-ety of Safety Engineers (ASSE), International Safety Equipment Association (ISEA), Na-tional Safety Council (NSC), American Feder-ation of Labor and Congress of Industrial Or-ganizations (AFL–CIO), and NanoBusiness Commercialization Association (NanoBCA).

2.4 NIOSH Research CapabilitiesWithin its divisions, NIOSH has world-re-nowned researchers who are trained and expe-rienced in the full spectrum of scientific skills needed to evaluate and characterize workplace hazards and devise intervention strategies for protecting workers. In addition to this exper-tise, NIOSH has significant laboratory capa-bilities in particle measurement, aerosol col-lection and characterization, particle surface analysis, measurement of particle surface rad-icals and activity, and in vitro and in vivo anal-ysis of toxicity and pathogenesis. Laboratories conducting nanomaterial research are locat-ed in Cincinnati, Ohio; Pittsburgh, Pennsylva-nia; and Morgantown, West Virginia. NIOSH researchers work closely with a broad range of scientists from industry, academia, and oth-er government agencies. The involvement of NIOSH in national and international initia-tives and programs is an important component of its capacity to address critical occupational safety and health issues in nanotechnology.

2.5 NIOSH Partnerships NIOSH recognizes both the practical need and the leadership obligation to extend its internal capabilities by leveraging activities and expertise found in other research institutions, industries,

http://www.cdc.gov/niosh/nora


federal agencies, and nongovernmental organi-zations. These partnerships serve to deliver on multiple objectives; most important, they add to the body of knowledge on workplace health and safety issues associated with nanotechnolo-gy. Partnerships have taken several forms, rang-ing from formal letters or memoranda of un-derstanding to informal working agreements on a specific topic. NIOSH will continue to pursue partnerships as a means of achieving the goals of this strategic research plan and as ef-fective vehicles to develop and disseminate re-search results.

The NIOSH NTRC has successfully used part-nerships with industry to gain a better under-standing of actual industrial nanomaterial pro-cesses, workplace exposures, work practices, and exposure control techniques. The field research conducted by the NTRC to assess exposures to engineered nanoparticles represents ongoing part-nerships with numerous companies. The NTRC will continue to develop these partnerships to

• better understand how engineered nanoparticles are being produced and used

• develop recommendations for the safe handling of nanomaterials

• develop sampling and analytical methods • evaluate exposure controls that are or

could be used in nanomaterial processes • evaluate the need for and determine the

effectiveness of PPE, including respira-tory protection

• develop communication and informa-tion materials that will assist industry in communicating with workers and the public.

Several of the industrial partnerships have pro-vided opportunities for the NTRC to identi-fy areas in which additional research is needed.

The continued collaboration with other na-tional and international research institutes, ac-ademia, and government agencies provides the NTRC the opportunity to combine its exper-tise in workplace health and safety with the capabilities of other organizations to investi-gate specific areas of concern. Working rela-tionships with other research institutes pro-vide the NTRC with the information needed to guide its own research, focus its limited re-sources effectively, and expand its research ca-pabilities through scientific collaboration. The NTRC has developed partnerships in the ar-eas of toxicology, risk assessment modeling, ex-posure measurement methods, epidemiology, industrial hygiene, control technologies, filtra-tion of nanoparticles, and communication of research results and safe work practices.

The NTRC has broadened its activities with collaborators and stakeholders by participating in a number of national and international com-mittees and working groups. This participation provides NTRC scientists the opportunity to provide and receive input on the key research that is needed to address priority areas.


3 ACTIVITIES

3.1 NIOSH Nanotechnology Research Center (NTRC)

Vision of the NTRCThe vision of the NTRC is as follows:

Safe nanotechnology by delivering on the Na-tion’s promise—safety and health at work for all people through research and prevention.

Mission of the NTRCThe mission of the NTRC is to provide nation-al and world leadership for research and guid-ance on the implications of nanoparticles and nanomaterials for work-related injury and ill-ness, and the application of nanoparticles and nanomaterials in occupational safety and health.

3.2 NTRC Steering CommitteeThe NTRC Steering Committee is chaired by the NTRC Coordinator. The committee is made up of the program manager, program coordina-tor, program assistant coordinator, and critical area coordinators for each of the 10 research areas (some areas have multiple research coordinators). The steering committee is responsible for guid-ing NIOSH scientific and organizational plans in nanotechnology research (including coordina-tion for science and budget) and for developing strategic goals and objectives and performance measures for the NTRC. Regular updates and progress reports on internal research activities are managed through biweekly teleconferences among members of the NTRC Steering Com-mittee. In addition, to ensure the responsiveness, relevance, and impact of the NIOSH nanotech-nology program, members of the NTRC and ap-propriate stakeholders meet in person every 2 years at a scientific exchange meeting.

3.3 Current NIOSH NTRC Intramural Nanotechnology Research Activities

Current NIOSH NTRC research activities in nanotechnology are focused on occupational safety and health implications and applications of ENMs. Data gathered from ongoing research studies with engineered nanoparticles are used to better understand workplace nanoparticle ex-posures, the hazards posed by nanomaterials, and the potential risk of adverse health effects from occupational exposures. Studies are also providing data on the characteristics of nano-materials produced and used in the workplace, routes of exposure, and the effectiveness of work practices and engineering controls in preventing worker exposure. Findings from these intramu-ral studies are providing scientific data to sup-port the development of occupational safety and health recommendations. NIOSH progress and accomplishments in nanotechnology research can be found in the report Filling the Knowl-edge Gaps for Safe Nanotechnology in the Work-place [NIOSH 2012a].

3.3.1 Evaluation of the nanotechnology research program

NIOSH evaluates its research progress in nan-otechnology through a series of internal and external reviews. Past reviews of its nanotech-nology research program have been conduct-ed by the National Academies and by a work-group of scientists chaired by two members of the NIOSH Board of Scientific Counselors. Based on these reviews, a revised strategic plan was published in November 2009 that proposed focused research and guidance on (1) identi-fying categories of nanomaterials that can be distinguished by their physical and chemical


properties; (2) recommending specific expo-sure limits for various nanomaterials; (3) assess-ing hazards, risks, and exposures; and (4) devel-oping intervention strategies [NIOSH 2009b]. In addition to external reviews, NIOSH con-tinues to conduct annual program reviews and regular project reviews, and it publishes period-ic progress reports describing ongoing research and accomplishments.

This NIOSH Nanotechnology Research and Guid-ance Strategic Plan was reviewed by a workgroup of scientists chaired by two members of the NIOSH Board of Scientific Counselors, and public comment was solicited through an an-nouncement in the Federal Register.

3.4 Current NIOSH Extramural Nanotechnology Research Activities

The NIOSH Office of Extramural Pro-grams (OEP) manages the competitive pro-cess for awarding occupational safety and health grants and cooperative agreements to the research community outside the Insti-tute. This process involves peer review, pro-gram relevance, and priorities of the Nation-al Occupational Research Agenda (NORA), the NIOSH Research to Practice (r2p) ini-tiative, congressional mandates, and sector,

cross-sector, or coordinated emphasis areas of the NIOSH Program Portfolio (http://www.cdc.gov/niosh/programs).

Since 2001, the NIOSH OEP has fund-ed nanotechnology research through Occupa-tional Safety and Health Research Program Announcements (R01), Mentored Scientist Grants (K01), Small Research Grants (R03), Developmental Grants (R21), and Small Busi-ness Innovation Research Grants (R43/44). During the period 2001 to 2012, the NIOSH OEP has committed approximately $12 mil-lion to extramural nanotechnology research.* Summaries of the projects funded by the NIOSH OEP are included in the document Filling the Knowledge Gaps for Safe Nanotechnol-ogy in the Workplace [NIOSH 2012a]. Through continued collaboration with the Environmen-tal Protection Agency/National Center for En-vironmental Research (EPA/NCER), National Science Foundation (NSF), National Institutes of Health/National Institute of Environmental Health Sciences (NIH/NIEHS), and interna-tional agencies, the NIOSH OEP continues to support nanotechnology research that focuses on occupational safety and health issues. In ad-dition, the NIOSH OEP routinely confers with the NIOSH NTRC regarding research needs.

*This includes all extramural projects that involve any as-pect of nanotechnology.

http://www.cdc.gov/niosh/programs

http://www.cdc.gov/niosh/programs


4 GOALS

4.1 Address Each Element in the Risk Management Continuum

Ultimately, the goal of the NTRC is to develop information, knowledge, and guidance to pro-tect the nanotechnology workforce. It is rela-tively early in the emergence of nanotechnolo-gy and there are many gaps in knowledge, yet nano-enabled products are in commerce and workers are being exposed to nanomaterials. Consequently, there is a need to address all ele-ments in the risk management continuum con-currently.

The process for managing potential workplace exposures to engineered nanoparticles during their synthesis, manufacture, and incorporation into new materials and devices consists of the following steps to ascertain the appropriate risk management strategy:

1. identifying and characterizing the health and safety hazard;

2. conducting dose-response risk assess-ment;

3. assessing the extent of exposure; 4. characterizing the risk on the basis of

exposure; and 5. developing control and management

procedures [Schulte et al. 2008b].

As exposure assessment data for nanomateri-als become available, the existence of any occu-pational risk—and the conditions under which exposure to the hazard would be harmful to workers—can be determined. A goal of the risk characterization is to determine wheth-er exposure to a type of material (in this case, nanomaterials) used in a given technology is likely to result in adverse health effects. Ex-posure assessment data provide a means to

determine whether workers might be exposed and what type of control strategy might be ef-fective in preventing exposure. Epidemiologic research is needed to provide etiologic evidence for new hazards and quantitative exposure–re-sponse information for recommended exposure limits. Decisions about which nanomaterials to study epidemiologically require collecting infor-mation on workforce size, exposure levels, and expected hazard (from toxicological or other in-formation). The NIOSH NTRC is involved in conducting research and answering questions posed in each element of the risk management process to address knowledge gaps in the pro-tection of workers (Figure 7).

A challenge of the NIOSH NTRC program is to determine how to conduct timely research that addresses the elements of hazard identifi-cation through risk management, as introduc-tion of nanomaterials to the workplace contin-ues and the workforce exposed to them becomes more diversified. The approach taken by the NTRC has been to conduct concurrent, focused research to address knowledge gaps in each step of the risk management process to provide oc-cupational safety and health guidance.

4.2 Identification of NTRC Data Needs for Knowledge Gaps

In preparing this strategic plan, the NTRC steering committee met in spring 2012 to iden-tify data needs and research gaps. Information was gleaned from various sources:

• research studies conducted by the NIOSH NTRC and others

• comments received during public review from open meetings or submitted to the NIOSH Docket on Interim Guidance for


Hazard Identification“Is there reason to believe

this could be harmful?”

Risk Management“Develop procedures to minimize exposures”.

Hazard Characterization“How and under what

conditions could it be harmful?”

Exposure Assessment“Will there be exposure in

real-world conditions?”

Risk Characterization“Is substance hazardous

and will there be exposure?”

• Toxicologic research• Health effects assessment• Safety research

• Toxicologic research• Field assessment• Epidemiologic and hazard

surveillance research

• Metrology research• Field assessment• Control technology research• Personal protective equipment

(PPE) research

• Risk assessment• Dose-response modeling• Exposure characterization• Epidemiologic research

• Risk communication• Guidance development for

controls, exposure limits, PPE,and medical surveillance

• Information dissemination• Adherence investigation

Gaps in theProtection of Workers NIOSH Focus

Adapted from Gibbs [2006] and NRC [2009].

Figure 7. Addressing knowledge gaps in protecting nanomaterial workers.


Medical Screening and Hazard Surveil-lance for Workers Potentially Exposed to Engineered Nanoparticles

• comments received during public review from open meetings or submitted to the NIOSH Docket on Current Intelligence Bulletin for Occupational Exposure to Car-bon Nanotubes and Nanofibers

• comments received in the NIOSH Dock-et on the draft strategic goals [76 Fed. Reg.* 123612]

• the 2011 NEHI Environmental, Health, and Safety (EHS) Research Strategy

• various scientific meetings and collabo-rations, including tripartite attendance (labor, industry, and government) and stakeholder input workshops.

On the basis of this information, the following data needs and research gaps have been identified.

Increase understanding of new hazards and re-lated health risks to nanomaterial workers

• Identify emerging commercial ENMs through market forecasting and research, technology surveillance, and partner and stakeholder input.

• Determine how workers might be ex-posed to nanoparticles during manufac-turing, handling, and use of nanomaterials.

— Expand research from primary manufacturer to second-, third-, and fourth-generation use of ENMs.

— Continue field investigations to bet-ter understand worker exposures throughout the life cycle, including processing of nano-enabled products.

— Determine how ENMs interact with the body’s systems.

— Determine relationships between specific physicochemical properties of ENMs and adverse biological effects.

*Federal Register.

Expand understanding of the initial hazard findings of engineered nanomaterials

• Determine carcinogenicity of carbon nano-tubes (CNTs).

• Determine whether the cardiovascular sys-tem is more sensitive than the lungs to ef-fects from ENM exposures.

• Determine whether ENMs cause im-mune dysfunction.

• Explore the usefulness of biomarkers for identifying and determining the extent of worker exposure and the potential for adverse health effects.

• Conduct research on measurement meth-ods for nanomaterials.

— Align laboratory and field exposure metrics and measurement techniques.

— Expand and refine workplace mea-surement techniques for assessing exposure (tiered approach).

— Develop a microscopy method for CNTs and other ENMs.

— Identify the critical reference materi-als needed for measurement.

• Continue to evaluate additional ENMs for dustiness, explosibility, flammability, and electromagnetic hazard potential.

— Correlate dustiness, explosion, fire, and electromagnetic data with exist-ing hazard indexes.

Support the creation of guidance materials to inform nanomaterial workers, employers, health professionals, regulatory agencies, and decision-makers about the hazards, risk, and risk management approaches.

• Develop categorical and specific occupa-tional exposure limits.

— Conduct research to recommend specific exposure limits for various ENMs (e.g., nanosilver, graphene, carbon black, nano silica, nanoceram-ics, nano clays, nano catalysts), and


evaluate the adequacy of existing ex-posure limits.

• Identify categories of nanomaterials that can be distinguished by physicochemical parameters.

• Conduct risk assessments. — Nanoparticle lung dosimetry mod-

eling — Categorization and comparative po-

tency methods • Link risk assessment, toxicology, expo-

sure measurement, and control strategies. • Demonstrate effective risk management

practices. • Develop guidance materials.

— Update guidance for medical surveil-lance (include sensitivity and speci-ficity of medical tests).

— Evaluate and provide guidance on control technology.

— Integrate Prevention through Design (PtD) into ENM risk management guidelines.

— Use categorical approaches for ENMs to develop guidance on controlling exposures (hazard and control band-ing).

— Evaluate and provide guidance on PPE for use with ENMs.

• Partner with businesses to promote safe and responsible handling of ENMs.

• Determine whether there are potential ap-plications of nanomaterials for safety and health (e.g., improved sensors or PPE).

Support epidemiologic studies for nanomate-rial workers, including medical, cross-section-al, prospective cohort and exposure studies.

• Conduct epidemiologic research on the health of nanomaterial workers by em-ploying both cross-sectional and pro-spective designs.

• Partner with other U.S. agencies and groups that have begun epidemiologic and other surveillance studies.

• Determine appropriate tools for medi-cal screening and mechanisms of medical surveillance among workers exposed to specific EMNs.

• Create an exposure database that harmo-nizes with global exposure databases.

Assess and promote national and internation-al adherence with risk management guidance

• Conduct a national assessment to de-termine the extent of use of nanomate-rial exposure controls and any barriers to their use.

• Provide intervention strategies for indus-try sectors where adherence to good risk-management practices is low.

• Partner with other businesses, U.S. agen-cies, and the international community to promote safe, responsible development of nanomaterials.

4.3 Coalescing Priorities for NIOSH NTRC Research and Guidance for FY2013–FY2016

The NIOSH NTRC has proposed specific re-search activities (see Section 4.5) for FY2013–FY2016 that address the previously identified research needs and gaps (Section 4.2). Figure 8 provides a schema for how NIOSH will fo-cus its research activities in accordance with the goals of the NTRC Strategic Plan:

• Increase understanding of new hazards and related health risks to nanomaterial workers.

• Expand understanding of the initial haz-ard findings of engineered nanomaterials.

• Support the creation of standards and guid-ance materials to inform nanomaterial workers, employers, health professionals, regulatory agencies, and decision-makers


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• Support epidemiologic studies for nano-material workers, including medical, cross-sectional, prospective cohort, and exposure studies.

• Assess and promote national and inter-national adherence with risk manage-ment guidance.

The overall focus of the strategic plan will be to continue to generate data, information, and knowledge to protect the nanotechnology workforce, by using effective risk management techniques and particularly keeping exposure below occupational limits. Research is proposed to develop and update good risk-management practices, including categorical and specif-ic exposure limits. Research data and informa-tion will be cataloged and shared via informat-ics (resources, devices, and methods required to optimize the acquisition, storage, retrieval, and use of information).

4.4 Coordination with the National Nanotechnology Initiative

NIOSH research priorities address many of the strategic goals proposed by the NNI Strategy for Nanotechnology Environmental, Health, and Safety Research. Table 1 shows the align-ment of the NIOSH NTRC strategic goals and 10 NTRC critical research areas with the NNI EHS priority research needs (Appendix A).

4.5 Proposed NIOSH NTRC Research

The following proposed research for FY2013–FY2016 has been coalesced to focus on specif-ic research needs to fill data gaps (see Section 4.2) and the EHS priority research needs of the NNI (see Section 4.4). As knowledge gaps are filled and as resources become available, these research priorities could change.

Strategic Goal 1 (PPNANSG1): Increase un-derstanding of new hazards and related health risks to nanomaterial workers.

Intermediate Goal 1.1 (PPNANIG1.1): Conduct market forecasting and review available sur-veillance data to determine emerging commer-cial ENMs and next-generation uses of exist-ing ENMs.

Activity/Output Goal 1.1.1 (PPNANAOG1.1.1): Prioritize high-volume emerging ENMs to identify the next candidates for toxicological testing and field evaluation of workplace expo-sures.

Performance Measure 1.1.1: In FY2013, com-plete an initial market research and forecasting report for internal use. Update the report with-in 3 years.

Activity/Output Goal 1.1.2 (PPNANAOG1.1.2): Complete a secondary market analysis on high volume nanomaterials.

Performance Measure 1.1.2: By FY2014, complete a market landscape analysis of formu-lators and users of nano titanium dioxide, silver, graphene and cellulose. Identify key industries using these materials in current products and those to be commercialized in the near term.

Intermediate Goal 1.2 (PPNANIG1.2): Conduct research to contribute to the understanding of the toxicology and internal dose of emerging ENMs.

Activity/Output Goal 1.2.1 (PPNANAOG1.2.1): Evaluate acute and chronic effects in the lungs and in other organ systems and tissues. Deter-mine dose-response and time-course relation-ships. Determine rates of clearance of these nanoparticles after pulmonary exposure and translocation to systemic organs; characterize systemic effects.

Performance Measure 1.2.1: Complete tox-icologic studies on ENMs such as nanosilver, graphene, and nanocellulose; present the data via the Society of Toxicology and publish in the peer-reviewed literature by FY2016.


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g of

the

initi

al

haza

rd fi

ndin

gs o

f en

gine

ered

nan

oma-

teria

ls

Supp

ort t

he c

reat

ion

of g

uid-

ance

mat

eria

ls to

info

rm

nano

mat

eria

l wor

kers

and

em

ploy

ers

abou

t haz

ards

, ris

ks, a

nd ri

sk m

anag

emen

t ap

proa

ches

Supp

ort e

pide

mio

logi

c st

udie

s fo

r nan

omat

eria

l w

orke

rs, i

nclu

ding

med

i-ca

l, cr

oss–

sect

iona

l, pr

o-sp

ectiv

e co

hort

, and

ex-

posu

re s

tudi

es

Asse

ss a

nd p

rom

ote

natio

nal a

nd in

tern

a-tio

nal a

dher

ence

with

ris

k m

anag

emen

t gu

idan

ce

Toxi

city

and

inte

rnal

dose

*

3-RN

1†

3-RN

23-

RN3

3-RN

43-

RN5

4-RN

1

3-RN

1†

3-RN

23-

RN3

3-RN

43-

RN5

Mea

sure

men

t met

hods

1-RN

11-

RN2

1-RN

32-

RN1

3-RN

2

1-RN

11-

RN2

1-RN

32-

RN1

3-RN

2


Tabl

e 1

(Con

tinue

d). A

lignm

ent o

f Crit

ical

Res

earc

h Ar

eas

with

the

Five

Str

ateg

ic G

oals

of t

he N

IOSH

NTR

C an

d th

e NN

I EHS

Prio

rity

Rese

arch

Nee

ds (R

Ns)

(con

tinue

d)

NIOS

H NT

RC S

trat

egic

Goa

l/ Cr

itica

l Res

earc

h Ar

eaIn

crea

se u

nder

stan

d-in

g of

new

haz

ards

an

d re

late

d he

alth

ris

ks to

nan

omat

eria

l w

orke

rs

Expa

nd u

nder

stan

d-in

g of

the

initi

al

haza

rd fi

ndin

gs o

f en

gine

ered

nan

oma-

teria

ls

Supp

ort t

he c

reat

ion

of g

uid-

ance

mat

eria

ls to

info

rm

nano

mat

eria

l wor

kers

and

em

ploy

ers

abou

t haz

ards

, ris

ks, a

nd ri

sk m

anag

emen

t ap

proa

ches

Supp

ort e

pide

mio

logi

c st

udie

s fo

r nan

omat

eria

l w

orke

rs, i

nclu

ding

med

i-ca

l, cr

oss–

sect

iona

l, pr

o-sp

ectiv

e co

hort

, and

ex-

posu

re s

tudi

es

Asse

ss a

nd p

rom

ote

natio

nal a

nd in

tern

a-tio

nal a

dher

ence

with

ris

k m

anag

emen

t gu

idan

ce

Exp

osur

e ass

essm

ent

2-RN

12-

RN3

3-RN

24-

RN1

5-RN

2

2-RN

12-

RN3

3-RN

24-

RN1

5-RN

2

Epi

dem

iolo

gy an

d su

rvei

l-lan

ce

2-RN

12-

RN3

2-RN

43-

RN6

5-RN

2

5-RN

2

Risk

asse

ssm

ent

5-RN

15-

RN2

5-RN

5

5-RN

15-

RN2

5-RN

5

5-RN

35-

RN4


*A ch

eck

mar

k (

) ind

icate

s tha

t a g

oal i

s cur

rent

ly b

eing

addr

esse

d by

pro

jects

with

in th

e NIO

SH cr

itica

l res

earc

h ar

ea.

† Alp

hanu

mer

ic id

entifi

catio

ns in

dica

te sp

ecifi

c NN

I prio

rity

rese

arch

nee

ds (s

ee A

ppen

dix

A) b

eing

met

by

the N

IOSH

pro

jects

in ea

ch cr

itica

l res

earc

h ar

ea.

‡ Inte

rnat

iona

l eng

agem

ent i

s a p

riorit

y of t

he N

NI a

nd a

criti

cal c

ompo

nent

of t

he 2

011

NN

I EH

S Re

sear

ch S

trate

gy. H

owev

er, it

is n

ot id

entifi

ed as

a re

sear

ch n

eed

in th

e NN

I Stra

tegy

.§ N

IOSH

will

wor

k wi

th o

ther

gov

ernm

ents

to d

eter

min

e glo

bal a

dher

ence

. ¶ Th

e NN

I EH

S pl

an d

oes n

ot ad

dres

s app

licat

ions

of n

anom

ater

ials

for E

HS

use.

How

ever

, the

NN

I stra

tegi

c plan

inclu

des a

pplic

atio

ns as

a dr

ivin

g fo

rce b

ehin

d se

vera

l Fed

eral

nano

-te

chno

logy

pro

gram

s, an

d it

has t

he p

oten

tial t

o im

prov

e saf

ety

and

healt

h, su

ch as

thro

ugh

the d

evelo

pmen

t of a

dvan

ced

sens

ors o

r PPE

.

NIOS

H NT

RC S

trat

egic

Goa

l/ Cr

itica

l Res

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h Ar

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crea

se u

nder

stan

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ards

an

d re

late

d he

alth

ris

ks to

nan

omat

eria

l w

orke

rs

Expa

nd u

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rd fi

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gine

ered

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oma-

teria

ls

Supp

ort t

he c

reat

ion

of g

uid-

ance

mat

eria

ls to

info

rm

nano

mat

eria

l wor

kers

and

em

ploy

ers

abou

t haz

ards

, ris

ks, a

nd ri

sk m

anag

emen

t ap

proa

ches

Supp

ort e

pide

mio

logi

c st

udie

s fo

r nan

omat

eria

l w

orke

rs, i

nclu

ding

med

i-ca

l, cr

oss–

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iona

l, pr

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ectiv

e co

hort

, and

ex-

posu

re s

tudi

es

Asse

ss a

nd p

rom

ote

natio

nal a

nd in

tern

a-tio

nal a

dher

ence

with

ris

k m

anag

emen

t gu

idan

ce

Eng

inee

ring

cont

rols

and

PPE

2-RN

15-

RN1

5-RN

2

2-RN

15-

RN1

5-RN

2

5-

RN2

Fire

and

expl

osio

n sa

fety

1-RN

5 1-

RN5

Rec

omm

enda

tions

an

d gu

idan

ce 5-

RN‡

5-RN

§

5-RN

¶

5-RN

2

Glo

bal c

ollab

orat

ions

‡

§

App

licat

ions

¶

Tabl

e 1

(Con

tinue

d). A

lignm

ent o

f Crit

ical

Res

earc

h Ar

eas

with

the

Five

Str

ateg

ic G

oals

of t

he N

IOSH

NTR

C an

d th

e NN

I EHS

Prio

rity

Rese

arch

Nee

ds (R

Ns)


Performance Measure 1.2.2: Identify probable combinations of nanomaterial uses and if fre-quent combinations are identified, conduct pre-liminary toxicologic evaluations to determine if synergistic effects occur by FY2016.

Intermediate Goal 1.3 (PPNANIG1.3): Deter-mine whether nanomaterial toxicity can be cat-egorized on the basis of physicochemical prop-erties and mode of action.

Activity/Output Goal 1.3.1 (PPNANAOG1.3.1): Systematically investigate the physical and chem-ical properties of particles that influence their toxicity (e.g., size, shape, surface area, solubility, chemical properties, and trace components).

Activity/Output Goal 1.3.2 (PPNANAOG1.3.2.): Determine the biological mechanisms for tox-ic effects (e.g., oxidant stress, dissolution, fibro-genicity, and hydrophobicity) and how the key chemical and physical factors may influence these mechanisms.

Activity/Output Goal 1.3.3 (PPNANAOG1.3.3): Integrate mechanistic models (including an-imal models and in vitro screening tests) for assessing the potential toxicity of new nano-materials, and provide a basis for developing predictive algorithms for structure/function re-lationships and comparative toxicity analyses for risk assessment. Determine whether toxico-logic data from new studies can be linked to ex-isting toxicologic data.

Performance Measure 1.3.1: By FY2016, de-termine whether ENMs can be categorized (hazard banded) on the basis of physicochemical properties and/or the toxicologic mode of action.

Intermediate Goal 1.4 (PPNANIG1.4): Con-duct nanomaterial workplace exposure assess-ments at sites developing, producing, or using emerging ENMs.

Activity/Output Goal 1.4.1 (PPNANAOG1.4.1): Collaborate with nanomaterial businesses to identify processes that may release nanomate-rials during manufacturing or use of ENMs.

Evaluate potential exposures and document risk mitigation processes.

Performance Measure 1.4.1.1: Complete a minimum of four field evaluations per year at facilities producing or using emerging ENMs. By FY2014, publish summary findings in a peer-reviewed journal.

Performance Measure 1.4.1.2: Evaluate ENM use and risk management practices at user fa-cilities across the life cycle, including secondary and tertiary facilities. By FY2015, publish sum-mary findings in a peer-reviewed journal.

Strategic Goal 2 (PPNANSG2): Expand un-derstanding of the initial hazard findings of engineered nanomaterials.

Intermediate Goal 2.1 (PPNANIG2.1): Conduct research to evaluate the adverse chronic effects of single-walled carbon nanotubes, multi-walled carbon nanotubes, and carbon nanofibers.

Activity/Output Goal 2.1.1 (PPNANAOG2.1.1): Conduct toxicologic testing to determine the potential of single-walled carbon nanotubes, multi-walled carbon nanotubes, and carbon nanofibers to have long-term pulmonary effects (fibrosis, lung cancer, mesothelioma).

Performance Measure 2.1.1: By FY2016, pub-lish a report on the carcinogenicity of carbona-ceous nanomaterials, based on completed carci-nogenicity-toxicology studies.

Intermediate Goal 2.2 (PPNANIG2.2): Deter-mine whether human biomarkers of nanomate-rial exposure and/or response can be identified.

Activity/Output Goal 2.2.1 (PPNANAOG2.2.1): Conduct research to determine whether blood, urine, or nasal lavage markers can accurately predict initiation and progression of adverse re-sponses to ENMs.

Performance Measure 2.2.1: By FY2017, pub-lish results of human biomarker studies.


Activity/Output Goal 2.2.2 (PPNANAOG2.2.2): Conduct research to determine whether car-diovascular or immune responses are sensitive indicators of pulmonary exposure to ENMs.

Performance Measure 2.2.2: By FY2016, pub-lish findings on cardiovascular and immune re-sponses to pulmonary exposure to ENMs.

Intermediate Goal 2.3 (PPNANIG2.3): De-termine the relevance of in vitro and in vivo screening tests to worker response to inhala-tion of ENMs.

Activity/Output Goal 2.3.1 (PPNANAOG 2.3.1): Evaluate the relationship of deposition patterns and biological responses to pulmonary bolus exposure (intratracheal instillation or pharyn-geal aspiration) vs. exposure extended over time (inhalation) of ENMs in rodent models.

Performance Measure 2.3.1: By FY2016, pub-lish findings on the relationship of deposition patterns and biological responses to pulmonary bolus exposure vs. exposure extended over time.

Activity/Output Goal 2.3.2 (PPNANAOG 2.3.2): Evaluate predictive in vitro screening tests for fibrogenicity, genotoxicity, and/or cell transfor-mation.

Performance Measure 2.3.2: Publish results from predictive in vitro screening tests for fibro-genicity, genotoxicity, and/or cell transformation, over the next 2 to 4 years (FY2014–FY2016).

Intermediate Goal 2.4 (PPNANIG2.4): Con-duct research on measurement methods for nanomaterials.

Activity/Output Goal 2.4.1 (PPNANAOG2.4.1): Continue interactions with national metrology institutes and qualify cellulose and single-walled CNT nanoscale reference materials (RMs) and/or benchmark materials for evaluating measure-ment tools, instruments, and methods for expo-sure assessment and toxicology.

Performance Measure 2.4.1.1: By FY2014, com-plete a round-robin evaluation of a transmission electron microscopy (TEM) sample-preparation procedure using National Institute of Stan-dards and Technology (NIST) gold nanoparti-cle RMs 8011, 8012, and 8013.

Performance Measure 2.4.1.2: By FY2014, translate this TEM sample-preparation proce-dure into a consensus standard practice or guide through ASTM International Committee E56: Nanotechnology.

Performance Measure 2.4.1.3: Within 4 years (FY2016), utilize NIST gold nanoparticle RMs 8011, 8012, and 8013 to evaluate filter- and grid-based sample-collection techniques and TEM analysis for spherical ENMs.

Performance Measure 2.4.1.4: By FY2016, develop measurement protocols for dynamic light scattering (hydrodynamic diameter), laser Doppler electrophoresis (zeta potential), and gas adsorption (surface area) measurements that utilize RMs (as appropriate) for particle characterization for internal use to promote re-producibility of testing.

Performance Measure 2.4.1.5: By FY2016, develop instrument sampling cards that pro-vide a succinct summary on the operation and utility of condensation particle counters, scan-ning mobility particle sizers, and diffusion chargers for internal use to promote measure-ment quality.

Activity/Output Goal 2.4.2 (PPNANAOG2.4.2): Understand relationships between laboratory instrumentation used to characterize aerosols for toxicology studies and field-measurement instrumentation used to characterize workplace atmospheres.

Performance Measure 2.4.2: By FY2016, com-plete a series of studies to evaluate test atmo-spheres with real-time and integrated labora-tory and field-measurement instruments for a range of metrics, including particle number, size, and surface area.


Activity/Output Goal 2.4.3 (PPNANAOG2.4.3): Conduct further research on the dustiness testing of powders and to benchmark the Venturi (Uni-versity of North Carolina) dustiness testing de-vice against a more traditional dustiness test (e.g., a standard method prescribed in EN 15051).

Performance Measure 2.4.3: By FY2015, com-pare the Venturi dustiness testing device against at least one other method for a range of fine and nanoscale materials.

Activity/Output Goal 2.4.4 (PPNANAOG2.4.4): Conduct further research on determining the advantages and limitations of direct reading in-struments in assessing nanoparticle work-place emissions and exposures.

Performance Measure 2.4.4: By FY2015, pub-lish at least one further study on the perfor-mance of direct reading instruments for assess-ing nanoparticle emissions or exposures in the workplace.

Activity/Output Goal 2.4.5 (PPNANAOG2.4.5): Develop and improve methods and approach-es (including direct reading and time-integrat-ed sampling) for assessing workplace exposures to ENMs.

Performance Measure 2.4.5.1: By FY2015, publish updated strategies for assessing work-place exposures.

Performance Measure 2.4.5.2: By FY2015, validate method 5040 for a series of CNT in-cluding. NIST Standard Reference Materi-al 248: Single-Wall Carbon Nanotubes (Raw Soot).

Activity/Output Goal 2.4.6 (PPNANAOG2.4.6): Evaluate scanning electron microscopy, trans-mission electron microscopy, and dark-field mi-croscopy as analytical tools for measurement of carbon nanotubes using NIST Standard Refer-ence Material 248: Single-Wall Carbon Nano-tubes (Raw Soot).

Performance Measure 2.4.6: By FY2015, pub-lish a microscopy method (or methods) for sample preparation, identification, and/or pos-sible semi-quantification that is applicable to some ENMs.

Activity/Output Goal 2.4.7 (PPNANAOG2.4.7): Conduct research to advance the use of nano-materials in the development of sensors (e.g., detection of harmful chemicals) and oth-er health and safety–related applications that can be used in the workplace to ensure effective control of exposure.

Performance Measure 2.4.7.1: By FY2016, develop an effective sensor employing nano-materials for the real-time measurement of a workplace agent, and publish the results.

Performance Measure 2.4.7.2: By FY2016, compile and publish a compendium on appli-cations of nanotechnology to improve work-place safety and health.

Intermediate Goal 2.5 (PPNANIG2.5): Con-duct research to better define the potential fire and explosion safety hazards of ENMs.

Activity/Output Goal 2.5.1 (PPNANAOG2.5.1): Identify physical and chemical properties that contribute to dustiness, combustibility, flam-mability, explosibility, and electromagnetic haz-ards of ENMs.

Performance Measure 2.5.1: By FY2014, pub-lish preliminary findings from explosibility test-ing of some ENMs.

Performance Measure 2.5.2: By FY2016, pub-lish findings that may influence the National Fire Protection Association (NFPA) or Depart-ment of Transportation (DOT) flammability placard information and the DOT Emergency Response Guidebook.

Intermediate Goal 2.6 (PPNANIG2.6): Devel-op and use informatics to process and commu-nicate information.


Activity/Output Goal 2.6.1 (PPNANAOG2.6.1): Create a harmonized database to share exposure measurement, control, and epidemiologic data.

Performance Measure 2.6.1: By FY2015, have a populated dataset containing NIOSH results on measurement, control, and epidemiologic data.

Activity/Output Goal 2.6.2 (PPNANAOG2.6.2): Lead the nanoinformatics community to devel-op an open literature monograph on nanoinfor-matics principles and practice.

Performance Measure 2.6.2: Complete and publish the nanoinformatics monograph by FY2015.

Strategic Goal 3 (PPNANSG3): Support the creation of guidance materials to inform nanomaterial workers, employers, health pro-fessionals, regulatory agencies, and decision-makers about hazards, risks, and risk man-agement approaches.

Intermediate Goal 3.1 (PPNANIG3.1): Develop categorical and specific exposure limits.

Activity/Output Goal 3.1.1(PPNANAOG3.1.1): Conduct a risk assessment for high-volume ENMs.

Performance Measure 3.1.1: By FY2015, com-plete a quantitative risk assessment (QRA) on ultrafine and fine materials from existing stud-ies. Evaluate QRA methods for nanomaterials. Start QRA for nanoparticles, with use of new NIOSH data. Use NIOSH nanoparticle data to calibrate and validate dosimetry models for nanoparticles.

Activity/Output Goal 3.1.2 (PPNANAOG3.1.2): Develop a risk-assessment framework for eval-uating the hazard and predicting the risk of ex-posure to ENMs.

Performance Measure 3.1.2: By 2017, devel-op a risk-assessment framework to rank haz-ard and estimate risk from exposure to selected ENMs in the workplace.

Activity/Output Goal 3.1.3 (PPNANAOG3.1.3): Use a nanomaterial hazard banding classifica-tion scheme to group ENMs.

Performance Measure 3.1.3: By FY2016, de-velop a hazard banding classification scheme for ENMs on the basis of toxicological, chemi-cal, and physical properties.

Intermediate Goal 3.2 (PPNANIG3.2): Con-duct research to better understand engineering controls and PPE for use with ENMs.

Activity/Output Goal 3.2.1 (PPNANAOG3.2.1): Evaluate the effectiveness of engineering con-trol techniques for ENMs and develop new ap-proaches as needed.

Performance Measure 3.2.1: Conduct field investigations of workplaces where ENMs are manufactured and used to evaluate existing en-gineering controls and make recommendations on improving exposure control. By FY2015, publish case studies and workplace survey re-ports, and by FY 2016, publish updated engi-neering control solutions.

Activity/Output Goal 3.2.2 (PPNANAOG3.2.2): Conduct laboratory evaluations of commercial-ly available engineering controls for a variety of common ENM production, handling, and downstream processes.

Performance Measure 3.2.2: By FY2016, pub-lish in-depth reports and journal articles on the effectiveness of the commercially available en-gineering control devices.

Activity/Output Goal 3.2.3 (PPNANAOG3.2.3): Evaluate the effectiveness of PPE (respirators, and protective clothing including gloves) for reducing worker exposures to ENMs.

Performance Measure 3.2.3: By FY2016, pub-lish updated guidance on the effectiveness of PPE for reducing worker exposures to ENMs.

Intermediate Goal 3.3 (PPNANIG3.3): Incor-porate Prevention through Design (PtD) into nanomaterial health and safety programs.


Activity/Output Goal 3.3.1 (PPNANAOG3.3.1): Promote PtD principles for nanomaterials, in-cluding safer nanomaterials that have the same functionality; process containment and con-trol; and management system approaches to in-clude occupational safety and health into the nanoparticle synthetic process, product devel-opment, and product manufacture.

Performance Measure 3.3.1: By FY2015, publish a document specific to PtD for nano-materials.

Intermediate Goal 3.4 (PPNANIG3.4): Foster the collection, management, and dissemination of relevant information to protect nanomateri-al workers.

Activity/Output Goal 3.4.1 (PPNANAOG3.4.1): Develop and disseminate effective information, education, and training materials to various tar-get audiences such as nanotechnology workers and employers, occupational safety and health professionals, policy-makers, decision-makers, and/or the scientific community.

Performance Measure 3.4.1.1: By FY2015, create nanomaterial guidance documents for workers, including small business and construc-tion workers.

Performance Measures 3.4.1.2: By FY2015, update Approaches to Safe Nanotechnology: Man-aging the Safety and Health Concerns Associated with Engineered Nanomaterials.

Performance Measures 3.4.1.3: By FY2016, up-date the Progress Report on the NIOSH Nano-technology Research and Communication Effort.

Performance Measure 3.4.1.4: Create new guidance documents on use of engineering con-trols, PPE, and PtD, as per Performance Mea-sures 3.2.1, 3.2.2, 3.2.3, and 3.3.1.

Performance Measure 3.4.1.5: By FY2016, support a conference on risk management of ENMs, with a focus on engineering controls.

Performance Measure 3.4.1.6: By FY2016, evaluate Nanomaterial Safety Data Sheets for adherence with the updated OSHA HazCom rule (including the use of Global Harmoniza-tion System), and issue guidance documents based on the updated findings.

Intermediate Goal 3.5 (PPNANIG3.5): Enhance global workplace safety and health through in-ternational activities.

Activity/Output Goal 3.5.1 (PPNANAOG3.5.1): Establish and maintain national and interna-tional partnerships so that knowledge gaps, re-search needs and priorities, approaches, and da-tabases could be shared.

Performance Measure 3.5.1.1: Strengthen co-ordination of research through government-level organizations such as the Organization for Economic Cooperation and Development (OECD) and United Nations (UN).

Performance Measure 3.5.1.2: By FY2015, expand collaborations to developing nations.

Activity/Output Goal 3.5.2 (PPNANAOG3.5.2): Improve sharing critical data globally.

Performance Measure 3.5.2.1: By FY016, de-velop a global portal for information on ENMs relevant to occupational safety and health.

Performance Measure 3.5.2.2: If feasible, by FY2016 initiate the development of a global exposure registry database.

Performance Measure 3.5.2.3: In FY2015, par-ticipate in OECD Nanomaterial Safety Testing Program by sponsoring nanomaterial testing and by data exchange.

Activity/Output Goal 3.5.3 (PPNANAOG 3.5.3): Lead the development of global standards on oc-cupational safety and health for nanotechnology.

Performance Measure 3.5.3.1: Over the next 3 years (FY2014–FY2016), lead the develop-ment of at least one standard in the Interna-tional Organization for Standardization.


Performance Measure 3.5.3.2: Over the next 3 years (FY2014–FY2016), lead the development of at least one guidance document for the UN.

Performance Measure 3.5.3.3: Over the next 3 years (FY2014–FY2016), lead the development of at least one guidance document for the OECD.

Strategic Goal 4 (PPNANSG4): Support epi-demiologic studies for nanomaterial workers, including medical, cross-sectional, prospec-tive cohort, and exposure studies.

Intermediate Goal 4.1 (PPNANIG4.1): Con-duct epidemiologic research and evaluate fea-sibility of conducting surveillance of nanoma-terial workers.

Activity/Output Goal 4.1.1 (PPNANAOG4.1.1): Complete the epidemiological health studies of U.S. workers exposed to CNTs and carbon nanofibers.

Performance Measure 4.1.1: By FY2016, complete data collection for industry-wide ex-posure and epidemiological studies of workers exposed to carbonaceous nanomaterials.

Activity/Output Goal 4.1.2 (PPNANAOG4.1.2): Evaluate the need for and feasibility of initiat-ing worker exposure registries for workers ex-posed to existing nanomaterials (e.g., titanium dioxide, CNTs) or producing and using new nanomaterials.

Performance Measure 4.1.2: By FY2016, de-velop a template and begin population of work-er exposure registries.

Activity/Output Goal 4.1.3 (PPNANAOG4.1.3): Integrate nanotechnology safety and health guidance into existing hazard surveillance sys-tems. Determine whether these systems are ad-equate by conducting evaluations.

Performance Measure 4.1.3: By FY2016, update NIOSH Current Intelligence Bulletin 60: Interim Guidance for the Medical Screen-ing and Hazard Surveillance of Workers Po-tentially Exposed to Engineered Nanoparticles [NIOSH 2009d].

Strategic Goal 5 (PPNANSG5): Assess and promote national and international adher-ence with risk management guidance.

Intermediate Goal 5.1 (PPNANIG5.1): Deter-mine the extent to which control measures are being adopted by industry. Identify any barriers to use of controls and partner with business to address barriers.

Activity/Output Goal 5.1.1 (PPNANAOG 5.1.1): Determine whether NIOSH or other precautionary guidance recommendations are being adopted by businesses.

Performance Measure 5.1.1: Within the next 3 years, conduct formal and informal assess-ments of the controls used in ENM-produc-ing or -handling facilities. By FY2016, publish findings.

Activity/Output Goal 5.1.2 (PPNANAOG 5.1.2): Develop a plan for industrial sectors where ad-herence to good risk-management practice is low.

Performance Measure 5.1.2: By 2016, publish a plan for intervening in industry sectors with low adherence to risk management guidance.

Activity/Output Goal 5.1.3 (PPNANAOG 5.1.3): Develop a follow-back program for the field in-vestigation activities.

Performance Measure 5.1.3: By 2014, have a follow-back program in place to determine if facilities are implementing suggestions from the field investigations.

Activity/Output Goal 5.1.4 (PPNANAOG 5.1.4): Support the International Commission on Oc-cupational Health (ICOH) and other orga-nizations in assessing whether precautionary guidance recommendations are being adopted worldwide.

Performance Measure 5.1.4: By 2016, sup-port ICOH in developing a plan to address lo-cations where adherence to good risk-manage-ment practice is low.


5 OUTPUTS

A summary of NIOSH NTRC research out-puts and accomplishments is presented in the report Filling the Knowledge Gaps for Safe Nano-technology in the Workplace [NIOSH 2012a].

5.1 NIOSH Publications on Nanotechnology Since 2009

NIOSH NTRC scientists will continue to de-velop documentation that provides guidance and technical information for workers, employ-ers, health professionals, regulatory agencies, and decision-makers in government, academia, industry, and labor. Examples of such documen-tation include the following:

• Current Intelligence Bulletin (CIB) 65, Oc-cupational Exposure to Carbon Nanotubes and Carbon Nanofibers, DHHS (NIOSH) Publication No. 2013–145 [NIOSH 2013]. This document includes a recommended exposure limit for carbon nanotubes and nanofibers. It is available at http://www.cdc.gov/niosh/docs/2013-145/.

• Filling the Knowledge Gaps for Safe Nan-otechnology in the Workplace, DHHS (NIOSH) Publication No. 2013–101 [NIOSH 2012a]. It is available at http://www.cdc.gov/niosh/docs/2013-101/.

• Current Intelligence Bulletin (CIB) 63, Oc-cupational Exposure to Titanium Dioxide, DHHS (NIOSH) Publication No. 2011–160 [NIOSH 2011]. This document in-cludes a recommended exposure limit for both fine and ultrafine (nano) titanium dioxide (TiO2). It is available at http://www.cdc.gov/niosh/docs/2011-160/.

• General Safe Practices for Working with Engineered Nanomaterials in Research Laboratories, DHHS (NIOSH) Publi-cation No. 2012–147 [NIOSH 2012b].

It is available at http://www.cdc.gov/niosh/docs/2012-147/ .

• NIOSH sponsored a supplement to the Journal of Occupational and Environmental Medicine, entitled Selected Papers from the Nanomaterials and Worker Health, Medi-cal Surveillance, Exposure Registries and Epidemiologic Research Conference, July 21–23, 2010 [ JOEM 53(6S):S1–S112].

• Progress Toward Safe Nanotechnology in the Workplace: A Report from the NIOSH Nanotechnology Research Center, DHHS (NIOSH) Publication No. 2010–104 [NIOSH 2009a]. This document reports on the status of nanotechnology research conducted by the NIOSH NTRC in 2007–2008. It is available at http://www.cdc.gov/niosh/docs/2010-104/.

• Approaches to Safe Nanotechnology: Manag-ing the Health and Safety Concerns Associat-ed with Engineered Nanomaterials, DHHS (NIOSH) Publication No. 2009–125 [NIOSH 2009c]. This document served a dual purpose of summarizing NIOSH’s current thinking and interim recommen-dations and fostering the exchange infor-mation to ensure that no worker suffers material impairment of safety or health as nanotechnology develops. It is available at http://www.cdc.gov/niosh/docs/2009-125/.

• Interim Guidance for Medical Screening and Hazard Surveillance for Workers Poten-tially Exposed to Engineered Nanoparticles, DHHS (NIOSH) Publication No. 2009–116 [NIOSH 2009d]. This document recommended prudent precautionary in-terim measures for reducing work-related exposures and assessing potential risk. It is available at http://www.cdc.gov/niosh/docs/2009-116/.















5.2 NIOSH Peer-Reviewed Publications

NIOSH NTRC scientists will continue to publish results of research as the data become available. More than 500 peer-reviewed articles were published between 2004 and 2012 that addressed scientific and technical issues in the field of nanotechnology. NIOSH will contin-ue to evaluate the utility of its publications and their impact on the scientific, regulatory, and occupational health community.

5.3 Sponsored ConferencesThe NIOSH NTRC will continue to partner with others in sponsoring and conducting con-ferences on nanotechnology. To date, NIOSH

has co-sponsored 15 international nanomate-rial health and safety meetings. NTRC staff members also have participated on several sci-entific and technical panels convened by gov-ernment agencies, nongovernmental agencies, and professional associations.

5.4 Presentations NTRC staff will continue to deliver presenta-tions nationally and internationally concerning occupational safety and health issues associat-ed with nanotechnology, including presenta-tions at scientific conferences and to trade and professional associations. To date, NTRC staff members have given more than 650 presenta-tions on nanomaterial health and safety topics.


6 RESEARCH TO PRACTICE (r2p)

Research to practice (r2p) involves the transla-tion of research into products, practices, and us-able information. The NIOSH NTRC nano-technology strategic plan reflects the r2p vision to work with partners and stakeholders to trans-late research findings into NIOSH products (e.g., guidance documents, instrumentation, nanopar-ticle filtration methods, and exposure controls) that will be used to reduce or prevent worker in-jury and illness from nanotechnology. R2p also involves moving others to action. NIOSH will continue to work with national and international organizations to translate research to actions that will protect the nanomaterial workforce.

6.1 Capacity Building through Technical Assistance

The NIOSH NTRC is currently collaborat-ing with a number of industries to develop

appropriate engineering controls and ef-fective administrative practices for the safe handling of nanomaterials. Specifically, the NTRC will continue to work with indus-try and labor in evaluating workplace expo-sures to ENMs and provide recommenda-tions that will minimize worker exposures. NIOSH has several complimentary re-sources that reside in the Health Hazard Evaluation, Industrywide Study, and Engi-neering Control Technology Programs that can provide expertise in augmenting ongo-ing NTRC efforts of evaluating workplace nanoparticle exposures, related health ef-fects, and risk management efforts.The NIOSH NTRC will continue to make rec-ommendations and provide information based on its research and findings report-ed in the published scientific literature. The recommendations will pertain to all areas of risk management described in Section 4.1.


7 INTERMEDIATE CUSTOMERS AND INTERMEDIATE OUTCOMES

7.1 Federal Government AgenciesNIOSH will conduct and coordinate research with other agencies to foster the responsible development and safe use of nanotechnology, as identified by the NNI. Specifically, NIOSH will continue to collaborate with OSHA, EPA, NIST, NIEHS, and the Consumer Product Safety Commission (CPSC).

7.2 Standards Development Organizations

NIOSH actively participates in the develop-ment of national and international standards for promoting the health and safety of workers in the nanotechnology industries. The NIOSH NTRC participates in the American Nation-al Standards Institute (ANSI) Nanotechnolo-gy Standards Steering Panel, which coordinates the identification and development of critical standards in all areas of nanotechnology.

NIOSH NTRC scientists also participate in the ASTM International E56 Committee on Nan-otechnology, which is developing an integrated family of standards. Committee E56.03 is ad-dressing environmental and occupational safe-ty and health.

NIOSH NTRC scientists will continue leading as chair and members of the U.S. Technical Ad-visory Group to the International Organization for Standardization (ISO) Technical Commit-tee 229 on Nanotechnologies (ISO TC 229). Work on instrumentation-related standards will continue with committees of the International Electrotechnical Commission (IEC).

NIOSH NTRC scientists will also contin-ue collaboration on the development of nano-technology-related guidance with authoritative bodies including the National Council on Radi-ation Protection and Measurements.

7.3 Industry, Labor, and Academia NIOSH is coordinating input from industry, labor, academics, and a wide range of govern-ment agencies in creating guidance for occu-pational health surveillance. Additionally, the NIOSH NTRC plans to coordinate input from those same groups of partners and stake-holders with the goal of developing standard-ized data systems for epidemiological research in workplaces producing and using nanoma-terials. Through collaborations with industry, government, and academia, NIOSH [2009c] has developed a “best practices” document, Approaches to Safe Nanotechnology: Managing the Health and Safety Concerns Associated with Engineered Nanomaterials [DHHS (NIOSH) Publication No. 2009–125; http://www.cdc.gov/niosh/docs/2009-125/] and will continue to develop other communication materials on the safe handling of ENMs. NIOSH NTRC is continuing to work with industry to character-ize occupational exposure to ENMs and im-plement effective risk-management practices to minimize worker exposure to ENMs.

7.4 Professional OrganizationsNIOSH is collaborating with various profes-sional organizations, including the American Industrial Hygiene Association (AIHA) and




National Safety Council (NSC), to identify mutual efforts for developing new worker train-ing programs.

7.5 Research CollaborationsNIOSH has established several national and international collaborations to advance re-search into the safe use of nanotechnology. The NIOSH NTRC participates in the National Nanotechnology Initiative (NNI) and has con-tributed to the nanotechnology environmental, health, and safety (EH&S) research strategy for the nation through the working group of Nan-otechnology Environmental and Health Impli-cations (NEHI). NIOSH’s strategic research plan and activities have been developed to ad-dress the occupational safety and health issues in the NSET/NEHI plan [NNI 2011].

7.6 International Activities NIOSH will continue to engage with a num-ber of international entities at all levels—as prin-ciple investigator as well as in national, region-al, and global organizations. At the national

organization level, the NIOSH NTRC has been communicating and collaborating with the United Kingdom Institute of Occupational Medicine and the Health and Safety Laborato-ry; the Netherlands Organization for Applied Scientific Research (TNO); the French Agen-cy for Food, Environmental and Occupational Health and Safety (ANSES); the Finnish In-stitute of Occupational Health; and the Aus-tralian Safety and Compensation Council (Safe Work Australia).

NIOSH is collaborating with the OECD to build cooperation, coordination, and commu-nication between the United States and 30 OECD member countries, including the Eu-ropean Union (EU), and more than 180 non-member economies. NIOSH is also work-ing with the UN World Health Organization (WHO); the UN International Labour Orga-nization (ILO); the International Organiza-tion for Standardization (ISO); the Interna-tional Electrotechnical Commission (IEC), the International Commission on Occupational Health (ICOH); and the International Coun-cil on Nanotechnology (ICON) on global proj-ects of information dissemination and commu-nication.


8 OUTCOMES

Nanotechnology is a rapidly developing area of science and technology that promises great ben-efits. To realize these benefits, it is important to protect workers potentially exposed to ENMs in nanomaterial research, production, and use [Schulte and Salamanca-Buentello 2007; Nas-terlack et al. 2008; Howard and Murashov 2009]. The NIOSH NTRC strategic plan is de-signed to identify and create the information needed for risk management programs that will control and prevent negative impacts on work-er health. Outcomes of the NIOSH NTRC re-search will be translated into products that can be used by the nanotechnology community to develop and implement appropriate risk man-agement practices to minimize worker exposure

to ENMs. NIOSH also will evaluate how re-search results and risk management guidance developed by NIOSH influence others to take action to prevent exposure to hazards related to ENMs.

NIOSH will assess the extent to which its re-search efforts have addressed each element of the risk management process (illustrated in Fig-ure 6) and determine how the outcomes of re-search have influenced others to take action to prevent exposure to hazards related to ENMs. NIOSH will publish a report of its research outcomes for the 2013–2016 period. A summa-ry of proposed research for FY2013–2014 and FY2015–2016 is shown in Appendix B


REFERENCES

Gibbs L [2006]. Presentation at the annual meeting of the Campus Safety Health and En-vironmental Management Association (CSHE-MA), Anaheim, CA, July 15–19.

Howard J, Murashov V [2009]. National nan-otechnology partnership to protect workers. J Nanopart Res 11:1673–1683.

ISO [2008]. Nanotechnologies: terminology and definitions for nano-objects—nanoparticle, nanofibre and nanoplate. ISO/TS 27687. Gene-va, Switzerland: International Organization for Standardization.

Murashov V, Schulte PA, Howard J [2012]. Progression of occupational risk management with advances in nanomaterials. J Occup Envi-ron Health 9:D12–D22.

Nasterlack M, Zober A, Oberlinner C [2008]. Considerations in occupational medical surveil-lance of employees handling nanoparticles. Int Arch Occup Environ Health 81:721–726.

NIOSH [2007]. Progress toward safe nano-technology in the workplace. Cincinnati, OH: U.S. Department of Health and Human Ser-vices, Centers for Disease Control and Preven-tion, National Institute for Occupational Safety and Health, DHHS (NIOSH) Publication No. 2007–123.

NIOSH [2009a]. Progress toward safe nano-technology in the workplace: a report from the NIOSH Nanotechnology Research Center. Cincinnati, OH: U.S. Department of Health and Human Services, Centers for Disease Control and Prevention, National Institute for Occu-pational Safety and Health, DHHS (NIOSH) Publication No. 2010–104.

NIOSH [2009b]. Strategic plan for NIOSH nanotechnology research and guidance. Cincin-nati, OH: U.S. Department of Health and Human

Services, Centers for Disease Control and Preven-tion, National Institute for Occupational Safety and Health, DHHS (NIOSH) Publication No. 2010–105.

NIOSH [2009c]. Approaches to safe nanotech-nology: managing the health and safety concerns associated with engineered nanomaterials. Cin-cinnati, OH: U.S. Department of Health and Human Services, Centers for Disease Control and Prevention, National Institute for Occu-pational Safety and Health, DHHS (NIOSH) Publication No. 2009–125.

NIOSH [2009d]. Interim guidance for medi-cal screening and hazard surveillance for work-ers potentially exposed to engineered nanopar-ticles. Cincinnati, OH: U.S. Department of Health and Human Services, Centers for Dis-ease Control and Prevention, National Institute for Occupational Safety and Health, DHHS (NIOSH) Publication No. 2009–116.

NIOSH [2011]. Current intelligence bulle-tin 63: occupational exposure to titanium di-oxide. Cincinnati, OH: U.S. Department of Health and Human Services, Centers for Dis-ease Control and Prevention, National Institute for Occupational Safety and Health, DHHS (NIOSH) Publication No. 2011–160.

NIOSH [2012a]. Filling the knowledge gaps: a report from the NIOSH Nanotechnology Re-search Center, from inception in 2004 through 2011. Cincinnati, OH: U.S. Department of Health and Human Services, Centers for Dis-ease Control and Prevention, National Institute for Occupational Safety and Health, DHHS (NIOSH) Publication No. 2013–101.

NIOSH [2012b]. General safe practices for work-ing with engineered nanomaterials in research laboratories. Cincinnati, OH: U.S. Depart-ment of Health and Human Services, Centers


for Disease Control and Prevention, National Institute for Occupational Safety and Health, DHHS (NIOSH) Publication No. 2012–147.

NNI [2001]. National Nanotechnology Initia-tive: interagency agreement. Washington, DC: United States Executive Office of the Presi-dent, Office of Science and Technology Policy [http://www.nano.gov/html/about/home_about.html].

NNI [2011]. National Nanotechnology Initia-tive: environmental, health, and safety research strategy. Washington, DC: United States Exec-utive Office of the President, Office of Science and Technology Policy, Nanotechnology En-vironmental and Health Implications (NEHI) Working Group.

NRC [2009]. Science and decisions:advancing risk assessment. Committee on improving risk analysis approaches used by the U.S. EPA, Board on Environmental Studies and Toxicolo-gy, Division on Earth and Life Studies, Nation-al Research Council of the National Academies.

NSF [2011]. Nanotechnology research direc-tions for societal needs in 2020: retrospective

and outlook summary. National Science Foun-dation. In: Roco M, Mirkin C, Hersan M, eds. Science Policy Reports. New York: Springer (DOI: 10.1007/978-94-007-1168-6_5).

Schulte, P, Geraci C, Zumwalde R, Hoover M, Castranova V, Kuempel E, Murashov V, Vainio H, Savolainen K [2008a]. Sharpening the fo-cus on occupational safety and health of nan-otech-nology. Scan J Work Environ Health 34(6):471–478.

Schulte P, Geraci C, Zumwalde R, Hoover M, Kuempel E [2008b]. Occupational risk man-agement of engineered nanoparticles. J Occup Environ Hyg 5:239–249.

Schulte PA, Salamanca-Buentello F [2007]. Ethical and scientific issues of nanotechnolo-gy in the workplace. Environ Health Perspect 115:5–12.

Schulte PA, Schubauer-Berigan MK, May-weather C, Geraci CL, Zumwalde R, McK-ernan JL [2009]. Issues in the development of epidemiologic studies of workers exposed to engineered nanoparticles. J Occup Environ Med 51(3):323–335.


Appendix A

Comprehensive Chart of the NNI 2011 EHS Research Needs[National Nanotechnology Initiative: Environmental, Health, and Safety Research Strategy. Washington, DC: United States Executive Office of the President, Office of Science and Tech-nology Policy, Nanotechnology Environmental and Health Implications (NEHI) Working Group, Table D–1.]

Protecting the Nanotechnology Workforce | 4140 | Protecting the Nanotechnology Workforce

Key Research Needs Subordinate Research Needs

1. Nanomaterial Measurement Infrastructure Research Needs

Develop measurement tools to detect and identify engineered nanoscale materials in products and rele-vant matrices and determine their physico-chemical properties throughout all stages of their life cycles.

Develop measurement tools for determination of biological response and to enable assessment of hazards and exposure for humans and the environment from engineered nanomaterials and nanotechnology-based products throughout all stages of their life cycles.

RN#1. Develop measurement tools for determination of physico-chemical properties of ENMs in relevant media and during the life cycles of ENMs and NEPs

• Physical dimensions and morphology: size, size distribution, char-acteristic dimensions, shape

• Internal structure: atomic-molecular, core-shell • Surface and interfacial properties: surface charge, zeta potential,

surface structure, elemental composition, surface-bound molecular coatings and conjugates, reactivity

• Bulk composition: elemental or molecular composition, crystalline phase(s)

• Dispersion properties: degree and state of dispersion • Mobility and other transport properties: diffusivity, transport in

biological and environmental matrices

RN#2. Develop measurement tools for detection and moni-toring of ENMs in realistic ex-posure media and conditions during the life cycles of ENMs and NEPs

• Sampling and collection of ENMs • Detecting the presence of ENMs • Quantity of ENMs-concentration based on surface area, mass, and

number concentrations • Size and size distribution of ENMs • Spatial distribution of ENMs • Discriminating ENMs from ambient NMs such as combustion

products and welding fumes • Discriminating multiple types of ENMs such as metals and metal

oxides

RN#3. Develop measurement tools for evaluation of transfor-mations of ENMs in relevant media and during the life cy-cles of ENMs and NEPs

• Agglomeration and de-agglomeration • Dissolution and solubility • Absorption of natural organic matter and bioconstituents • Oxidation and reduction • Deposition of ENMs on surfaces

(continued)

Table D–1. The Core EHS Research Categories and their Highest-Priority Research Needs (RNs)



RN#4. Develop measurement tools for evaluation of biolog-ical responses to ENMs and NEPs in relevant media and during the life cycles of ENMs and NEPs

• Adequacy of existing assays • New assays or high-throughput, high content assays • Correlation of biological responses with physico-chemical

properties • Surface reactivity at the interfaces between ENMs and biological

receptors • Biomarkers of toxicological response

RN#5. Develop measurement tools for evaluation of release mechanisms of ENMs from NEPs in relevant media and during the life cycles of NEPs

• Release by fire, combustion, and incineration • Release by mechanical degradation, such as abrasion, deformation,

and impact • Release by dissolution of matrix material • Release by chemical reactions of the matrix material • Release by photo-induced degradation of the matrix material • Release by consumer interactions, such as spraying, mouthing, and

swallowing • Release by interactions with biological organisms in the envi-

ronment

2. Human Exposure Assessment Research Needs

Identify potential sources, characterize the exposure scenarios, and quantify actual exposures of workers, the general public and consumers to nanomaterials.

Characterize and identify the health outcomes among exposed populations in conjunction with informa-tion about the control strategies used and exposures to determine practices that result in safe levels of ex-posure.

RN#1. Understand processes and factors that determine ex-posures to nanomaterials

• Conduct studies to understand processes and factors that deter-mine exposure to engineered nanomaterials

• Develop exposure classifications of nanomaterials and processes • Develop internationally harmonized and validated protocols for

exposure surveys, sample collection and analysis, and reporting through existing and newly created international frameworks

• Develop comprehension predictive models for exposures to a broad range of engineered nanomaterials and processes

• Characterize process- and task-specific exposure scenarios in the workplace

(continued)

Table D–1 (Continued). The Core EHS Research Categories and their Highest-Priority Research Needs (RNs)



RN#2. Identify population groups exposed to engineered nanomaterials

• Systematically collect and analyze information about nanomate-rial manufacture, processing, and direct use in commercial and consumer products over time to discern geographic areas where engineered nanomaterials may be emitted into the environment, consumed in the form of ingredients of products, and/or disposed of in solid waste, wastewater, etc.

• Conduct population-based surveys to obtain information on use patterns for consumer products

• Identify potential subpopulations that are more susceptible to exposure to engineered nanomaterials than others

• Develop quantitative assessment methods appropriate for target population groups and conduct assessments of those population groups most likely to be exposed to engineered nanomaterials

RN#3. Characterize individual exposures to nanomaterials

• Expand currently available exposure assessment techniques to facilitate more accurate exposure assessment for engineered nanomaterials at benchmark concentration levels using feasible methods

• Develop new tools through national and international surveys to support effective exposure characterization of individuals

• Characterize and detect nanomaterials in biological matrices and conduct studies to understand transformations of nanomaterials during transport in the environment and in human bodies

• Conduct studies to examine emissions and human contact during normal use and after wear and tear have degraded a product, as well as during repeated exposures

• Develop engineered nanomaterials exposure assessment models based on identified critical exposure descriptions

• Develop databases to contain the collected data and information

RN#4. Conduct health sur-veillance of exposed popula-tions

• Establish a program for the epidemiological investigations of physician case reports and reports of suspicious pattern of adverse events

• Establish exposure registry and medical surveillance programs for workers

• Analyze injury and illness reporting in existing programs

(continued)




3. Human Health Research Needs

Understand the relationship of physico-chemical properties of engineered nanoscale materials to in vivo physico-chemical properties and biological response.

Develop high-confidence predictive models of in vivo biological responses and casual physico-chemical properties of ENMs.

RN#1. Identify or develop ap-propriate, reliable, and repro-ducible in vitro and in vivo assays and models to predict in vivo human responses to ENMs

• Establish a system to develop and apply reliable and reproducible in vitro and in vivo test methods

• Evaluate the degree to which an in vitro response correlates with an in vivo response

• Evaluate the degree to which in vitro and in vivo models predict human response

• Translate structure-activity relationship and other research data into computational models to predict toxicity in silico

RN#2. Quantify and charac-terize ENMs in exposure ma-trices and biological matrices

• Determine critical ENM measurands in biological and environ-mental matrices and ensure the development of tools to measure ENMs in appropriate matrices as needed

• Determine matrix and/or weathering effects that may alter the physico-chemical characteristics of the ENM measurands

• Identify key factors that may influence the detection of each mea-surand in a particular matrix (e.g., sample preparation, detection method, storage, temperature, solvents/solutions)

• Characterize and quantify exposure for all exposure routes using in vivo models to identify the most likely routes of human exposure

• Identify biomarkers of exposure and analytical methods for their determination

RN#3. Understand the rela-tionship between the physico-chemical properties of ENMs and their transport, distribu-tion, metabolism, excretion, and body burden in the hu-man body

• Characterize ENM physico-chemical properties and link to mechanisms of transport and distribution in the human body

• Understand the relationship of the physico-chemical properties of ENMs to the mechanisms of sequestration in and translocation of ENMs out of the exposure organ and secondary organs, and to routes of excretion from the human body

• Determine the metabolism or biological transformation of ENMs in the human body

(continued)




RN#4. Understand the rela-tionship between the physico-chemical properties of ENMs and uptake through the human port-of-entry tissues

• Characterize ENMs at and in port-of-entry tissues, including nontraditional routes of entry such as the ear and eye, and identify mechanisms of ENM uptake into tissues

• Determine the relationship of ENM physico-chemical properties to deposition and uptake under acute exposure conditions and under chronic exposure conditions

• Translate data on ENM properties and uptake to knowledge that may be used to intentionally redesign ENMs for optimum human and environmental safety and product efficacy

RN#5. Determine the modes of action underlying the human biological response to ENMs at the molecular, cellular, tissue, organ, and whole body levels

• Determine the dose response and time course of biological responses at the primary site of exposure and at distal organs fol-lowing ENM exposure

• Understand the mechanisms and molecular pathway(s) associated with ENM biology within cellular, organ, and whole organism systems

• Link mechanisms of response with ENM physico-chemical prop-erties and employ this information in the design and development of future ENMs

• Develop translational alternative in vitro testing methods for the rapid screening of future ENMs based on mechanism(s) of response that are predictive of in vivo biological responses

RN#6. Determine the extent to which life stage and/or sus-ceptibility factors modulate health effects associated with exposure to ENMs and nan-otechnology-enabled products and applications

• Determine the effect of life stage and/or gender on biological response to ENMs

• Establish the role of genetic and epigenetic susceptibility on the biological response to ENMs in the context of life stage and/or susceptibility factors

• Understand mechanistically the influence of preexisting disease on the biological response to ENMs in the context of life stage and other susceptibility factors

• Identify exposure conditions that make susceptible individuals more vulnerable to the health effects associated with ENMs and nanotechnology-enabled applications

• Establish a database that contains published, peer-reviewed litera-ture, occupational and consumer reports, and toxicological profiles that describe altered responses to ENMs and nanotechnology-enabled applications in susceptible animal models or individuals following exposure

(continued)




4. Environment Research Needs

Understand the environmental fate, exposure, and ecological effects of engineered nanomaterials, with priority placed on materials with highest potential for release, exposure, and/or hazard to the environ-ment.

RN#1. Understand environ-mental exposures through the identification of principal sources of exposure and expo-sure routes

• Manufacturing processes and product incorporation • Life cycle of technology and exposures subsequent to product

manufacturing • Analytical approaches to measure temporal changes in nanopar-

ticle properties throughout the life cycle • Models to estimate releases • Environmental receptors for exposure assessment

RN#2. Determine factors af-fecting the environmental transport of nanomaterials

• Determine key physico-chemical properties affecting transport • Determine key transport and fate processes relevant to environ-

mental media • Develop new tools and adaptation of current predictive tools to

accommodate unique properties of nanomaterials

RN#3. Understand the trans-formation of nanomaterials under different environmental conditions

• Identify and evaluate nanomaterial properties and transformation processes that will reduce environmental persistence, toxicity, and production of toxic products

• Determine the rate of aggregation and long-term stability of agglomeration/aggregation and the long-term stability of these aggregates and agglomerates

• Develop tools to predict the transformations or degradability of nanomaterials

RN#4. Understand the effects of engineered nanomaterials on individuals of a species and the applicability of testing schemes to measure effects

• Test protocols • Dose-response characterization • Uptake/elimination kinetics, tissue/organ distribution • Mode/mechanism of action, predictive tools • Tiered testing schemes/environmental realism

RN#5. Evaluate the effects of engineered nanomaterials at the population, community, and ecosystem levels

• Population • Community • Other ecosystem-level effects • Predictive tools for population-, community-, and ecosystem-level

effects

(continued)




5. Risk Assessment and Risk Management Methods Research Needs

Increase available information for better decision making in assessing and managing risks from nanoma-terials, including using comparative risk assessment and decision analysis; life cycle considerations; and additional perspectives such as ELSI considerations, stakeholders’ values, and additional decision makers’ considerations.

RN#1. Incorporate relevant risk characterization informa-tion, hazard identification, ex-posure science, and risk mod-eling and methods into the safety evaluation of nanoma-terials

• Characterization, fate, and release of nanoparticles throughout the life cycles of nanotechnology-enabled products

• Development of predictive models on accumulation, migration, and release of nanoparticles throughout the life cycles of nano-technology-enabled products

• Safety of nanoparticles throughout the life cycles of the nanotech-nology-enabled products

• Comprehensive and predictive models to assess the potential risks of nanoparticles during the manufacturing and life cycle of nano-products, with inputs from human and environment exposures and on nanomaterial properties

RN#2. Understand, character-ize, and control workplace ex-posures to nanomaterials

• Dissemination and implementation of effective techniques and protocols to measure exposures in the workplace

• Identification and demonstration of effective containment and control technologies including for accidents and spills

• Development of an effective industry surveillance system • Design and deployment of a prospective epidemiological frame-

work relevant to exposure science • Systematic approaches for occupational risk modeling

RN#3. Integrate life cycle con-siderations into risk assessment

• Establishment of nanotechnology-specific taxonomy for life cycle stages

• Integration of risk assessment, life cycle analyses, and decision-making approaches into regulatory decision making processes

• Application of adaptive management tools based on monitoring/implementation to evaluate life cycle analysis implementation

• Development of case studies, e.g., green chemistry, nanomaterials selection, nanomaterials acquisition process, illustrating applica-tion of these risk management methods

(continued)




RN#4. Integrate risk assess-ment into decision-making frameworks for risk manage-ment

• Development of comparative risk assessment and formal decision-analytical methods as opposed to “absolute” risk assessment strate-gies

• Application of formal decision-analytical methods to prioritize risk management alternatives

• Use of gap analyses and value of information analysis to identify research needs

• Integration of stakeholder values and risk perceptions into risk management processes

• Application of integrated decision framework through case studies in risk management decision making

RN#5. Integrate and standard-ize risk communication with-in the risk management frame-work

• Development and use of standardized terminology in risk communications

• Early information-sharing on hazards and risk among Federal agencies

• Development of appropriate risk communication approaches for agency-specific needs

Informatics and Modeling Research Need

RN#1. Develop computation-al models of ENM structure- property-activity relationships to support the design and de-velopment of ENM with max-imum benefit and minimum risk to humans and the envi-ronment

• Validate the predictive capability of in vitro and in vivo assays and employ that subset of assays in data generation to establish computational models to predict ENM behavior in humans and the environment

• Establish a standard set of physical and chemical characterization parameters, dose metrics, and biological response metrics

• Design and establish structures and ontologies for methods devel-opment, data capture, sharing, and analysis

• Evaluate and adapt as necessary existing computational models by beginning with existing models for exposure and dosimetry and using data generated from validated assays

• Use ENM exposure and dosimetry models to develop ENM structure-activity models to predict ENM behavior in humans and the environment

• Establish training sets and beta test sites to refine and validate ENM structure-activity models

• Disseminate ENM structure-activity models through publicly ac-cessible nanotechnology websites



APPENDIX B

Timeline for NIOSH Nanotechnology Research

Summary of Proposed Research Projects, FY2013–FY2014

Critical research area Projects

Toxicity and Internal Dose

Evaluate long-term fibrogenic and carcinogenic potential of carbon nano-tubes and carbon nanofibers.

Determine immune and cardiovascular responses to pulmonary exposure to CNT, TiO2, and nanosilver.

Evaluate the pulmonary effects of nanosilver.

Measurement Methods Develop updated methods and approaches to assess occupational expo-sures to nanomaterials.

Utilize reference materials and technically sound protocols to improve measurement quality.

Develop techniques to characterize nanoparticles, using advanced micros-copy methods.

Study the performance of direct reading instruments for assessing emis-sions and exposure to nanoparticles in the workplace.

Exposure Assessment Complete evaluation of workplace exposures to emerging, second-generation, and third-generation ENMs and their potential routes of exposure.

Complete evaluation of size, concentration, and morphology of ENMs emitted by various processes.

Epidemiology and Surveillance

Evaluate occupational exposures among carbonaceous nanomaterial workers.

Complete field work for a cross-sectional epidemiologic survey among workers exposed to carbonaceous nanomaterials.

Collect data on specific biomarkers as markers of exposure or early health endpoints in workers exposed to carbon nanotubes or carbon nanofibers.

(continued)



Risk Assessment Develop a strategy and criteria to utilize the best available scientific data to develop hazard- and risk-based occupational exposure limits and other risk management guidance.

Identify nanomaterial categories by physicochemical properties and bio-logical mode of action, and perform case study evaluations for nanomate-rials within each major category.

Analyze toxicity data, including identifying the adverse health endpoint(s) and performing dose-response analyses and/or comparative potency analyses.

Contribute to the development and evaluation of dosimetry models and methods to assess internal dose of nanomaterials in workers.

Engineering Controls and PPE

Conduct field studies to assess and improve engineering control strategies in the workplace.

Evaluate effectiveness of commercially available engineering controls in the laboratory.

Finalize development of a standardized aerosol test method using mag-netic passive aerosol samplers for testing of protective clothing material.

Expand particulate penetration project to include evaluation of different types of fabrics, use of electrostatic charges, and bellows effects.

Evaluate balance between comfort and protection of protective clothing and gloves with ENMs.

Fire and Explosion Safety Evaluate nano metals and other ENMs for fire and explosion potential.

Evaluate a variety of ENMs for electromagnetic hazard potential.

Correlate dustiness of ENMs with various physical and chemical safety hazards.

Evaluate current DOT and NFPA guidance for adequacy with ENMs.

Provide recommendations to first responders about safety issues of ENMs.

Recommendations and Guidance

Continue conducting r2p activities (ongoing), such as developing bro-chures and fact sheets and updating the topic page.

Develop a small business guide for nanomaterial producers and users.


(continued)



Applications Further develop and refine end-of-service indicators using nanomaterials.

Global Activities Strengthen participation with globally recognized organizations ICON, ISO, OECD, and UN (WHO, ILO).

Participate in the US/EU nanomaterial working groups hosted by the NNI.



Summary of Proposed Research Projects for FY2015–FY2016


Toxicity and Internal Dose Identify biomarkers of response to ENMs.

Develop predictive algorithms for relationships between nanoparticle properties and bioactivity.

Determine the relevance of in vitro and in vivo screening tests.

Evaluate the pulmonary and systemic effects of graphene and nanocellu-lose.

Measurement Methods Publish updated exposure measurement methods.

Assist with round-robin evaluations of ENM reference materials.

Exposure Assessment Publish exposure results.

Provide guidance on exposure assessment methods and sampling proto-cols.

Epidemiology and Surveillance

Analyze biomarker samples from cross-sectional epidemiologic study of carbon nanotube and nanofiber workers.

Analyze data (medical and biomarker with exposure) from cross-sectional epidemiologic study of carbon nanotube and nanofiber workers.

Begin collecting data for exposure registry and prospective epidemiolog-ic study among carbon nanotube–exposed and carbon nanofiber–exposed workers.

Assess feasibility of epidemiologic study of health outcomes among work-ers exposed to nanomaterials other than carbonaceous nanomaterials.

Risk Assessment Extend evaluations of the hazard and risk of workplace exposure to new nanomaterials.

Utilize the latest data from toxicity studies, workplace exposure measure-ments, and/or biomonitoring data to identify potential hazards in the re-spiratory tract and/or other organs.

Contribute to the refinement and validation of dosimetry models for nanomaterials.

Contribute to the evaluation and development or updating of recom-mended exposure limits and other risk management guidance.

(continued)



Engineering Controls and PPE

Continue to assess engineering controls in the field and update recom-mendations for controlling exposure.

Continue to evaluate commercially available engineering controls in the lab and publish test results.

Evaluate respirator performance with ENMs in laboratory and workplace settings.

Develop a passive method for measuring particle penetration through protective clothing materials.

Fire & Explosion Safety Continue evaluation of various ENMs for fire and explosion potential.

Evaluate a variety of ENMs for electromagnetic hazard potential.

Correlate dustiness of ENMs with various physical and chemical safety hazards.

Publish findings in journals and provide summaries to DOT and NFPA.

Recommendations and Guidance

Update Approaches to Safe Nanotechnology

Develop hazard bands and RELs for high-volume commercially available ENMs.

Applications Evaluate ENM-enabled PPE.

Global Activities Lead or co-lead committees with globally recognized organizations: ICON, ISO, OECD, and UN (WHO, ILO).

NOTE: DOT, Department of Transportation; ENMs, engineered nanomaterials; ICON, International Council on Nanotechnology; ILO, International Labour Organization; ISO, International Organization for Standardization; NFPA, National Fire Protection Association; NNI, National Nanotechnology Initiative; OECD, Organization for Economic Cooperation and Development; PPE, personal protective equipment; UN, United Nations; WHO, World Health Organization.

Summary of Proposed Research Projects for FY2015–FY2016 (Continued)


NOTES


NOTES


NOTES

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DHHS (NIOSH) Publication No. 2014–106

safer • healthier • people™

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Documents

DEPARTMENT OF HEALTH AND HUMAN … Workforce ... Centers for Disease Control and Prevention, National Institute for Occupational Safety and Health, DHHS (NIOSH) Publication 2014–106